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Sample records for flow induced vascular

  1. Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo.

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    Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masatoshi; Ozaki, Hiroshi; Murata, Takahisa

    2015-01-01

    Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.

  2. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

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    Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: rmygxgwk@163.com [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)

    2014-11-07

    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

  3. Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-hui LI; Jun-bao DU; Ding-fang BU; Xiu-ying TANG; Chao-shu TANG

    2006-01-01

    Aim: To explore the possible role of endogenous hydrogen sulfide (H2S), a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling (PVSR) induced by high pulmonary blood flow. Methods: Thirty-two Sprague-Dawley male rats were randomly divided into sham, shunt, sham+NaHS (a H2S donor) and shunt+NaHS groups. Rats in shunt and shunt+NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt+NaHS and sham+NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase (NOS), heme oxygenase (HO-1), proliferative cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) activation were analyzed by Western blotting. Results: After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H2S production and an increase in nitric oxide (NO). However, lung tissue carbon monoxide (CO) did not change. After the treatment with NaHS for 11 weeks, H2S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats. Conclusions: H2S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H2S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.

  4. Heating in vascular tissue and flow-through tissue phantoms induced by focused ultrasound

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    Huang, Jinlan

    High intensity focused ultrasound (HIFU) can be used to control bleeding, both from individual blood vessels as well as from gross damage to the capillary bed. This process, called acoustic hemostasis, is being studied in the hope that such a method would ultimately provide a lifesaving treatment during the so-called "golden hour", a brief grace period after a severe trauma in which prompt therapy can save the life of an injured person. Thermal effects play a major role in occlusion of small vessels and also appear to contribute to the sealing of punctures in major blood vessels. However, aggressive ultrasound-induced tissue heating can also impact healthy tissue and can lead to deleterious mechanical bioeffects. Moreover, the presence of vascularity can limit one's ability to elevate the temperature of blood vessel walls owing to convective heat transport. In an effort to better understand the heating process in tissues with vascular structure we have developed a numerical simulation that couples models for ultrasound propagation, acoustic streaming, ultrasound heating and blood cooling in Newtonian viscous media. The 3-D simulation allows for the study of complicated biological structures and insonation geometries. We have also undertaken a series of in vitro experiments, in non-uniform flow-through tissue phantoms, designed to provide a ground truth verification of the model predictions. The calculated and measured results were compared over a range of values for insonation pressure, insonation time, and flow rate; we show good agreement between predictions and measurements. We then conducted a series of simulations that address two limiting problems of interest: hemostasis in small and large vessels. We employed realistic human tissue properties and considered more complex geometries. Results show that the heating pattern in and around a blood vessel is different for different vessel sizes, flow rates and for varying beam orientations relative to the flow axis

  5. Vascular calcification: Inducers and inhibitors

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    Lee, Donghyun, E-mail: dhlee@cau.ac.kr [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)

    2011-09-15

    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  6. Blood flow restricted exercise and vascular function.

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    Horiuchi, Masahiro; Okita, Koichi

    2012-01-01

    It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR) leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  7. Blood Flow Restricted Exercise and Vascular Function

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    Masahiro Horiuchi

    2012-01-01

    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  8. Diabetes and ageing-induced vascular inflammation.

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    Assar, Mariam El; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2016-04-15

    Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  9. Diabetes and ageing‐induced vascular inflammation

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    Assar, Mariam El; Angulo, Javier

    2015-01-01

    Abstract Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro‐inflammatory cytokines, vascular hyperactivation of nuclear factor‐кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti‐inflammatory microRNAs, and dysfunctional stress‐response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co‐exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low‐grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes‐induced vascular impairment in the elderly. PMID:26435167

  10. Surveillance of Hemodialysis Vascular Access with Ultrasound Vector Flow Imaging

    DEFF Research Database (Denmark)

    Brandt, Andreas Hjelm; Olesen, Jacob Bjerring; Lindskov Hansen, Kristoffer

    2015-01-01

    -functioning vascular access with as few complications as possible and preferred vascular access is an AVF. Dysfunction due to stenosis is a common complication, and regular monitoring of volume flow is recommended to preserve AVF patency. UDT is considered the gold standard for volume flow surveillance, but VFI has...... be used for surveillance of volume flow....

  11. Constructal Law of Vascular Trees for Facilitation of Flow

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    Razavi, Mohammad S.; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S.

    2014-01-01

    Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures. PMID:25551617

  12. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

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    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.

  13. Changes of blood flow, oxygen tension, action potential and vascular permeability induced by arterial ischemia or venous congestion on the spinal cord in canine model.

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    Kobayashi, Shigeru; Yoshizawa, Hidezo; Shimada, Seiichiro; Guerrero, Alexander Rodríguez; Miyachi, Masaya

    2013-01-01

    It is generally considered that the genesis of myelopathy associated with the degenerative conditions of the spine may result from both mechanical compression and circulatory disturbance. Many references about spinal cord tissue ischemic damage can be found in the literature, but not detailed studies about spinal cord microvasculature damage related to congestion or blood permeability. This study investigates the effect of ischemia and congestion on the spinal cord using an in vivo model. The aorta was clamped as an ischemia model of the spinal cord and the inferior vena cava was clamped as a congestion model at the 6th costal level for 30 min using forceps transpleurally. Measurements of blood flow, partial oxygen pressure, and conduction velocity in the spinal cord were repeated over a period of 1 h after release of clamping. Finally, we examined the status of blood-spinal cord barrier under fluorescence and transmission electron microscope. Immediately after clamping of the inferior vena cava, the central venous pressure increased by about four times. Blood flow, oxygen tension and action potential were more severely affected by the aorta clamping; but this ischemic model did not show any changes of blood permeability in the spinal cord. The intramedullar edema was more easily produced by venous congestion than by arterial ischemia. In conclusions, venous congestion may be a preceding and essential factor of circulatory disturbance in the compressed spinal cord inducing myelopathy.

  14. Nanoparticle-induced platelet aggregation and vascular thrombosis.

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    Radomski, Anna; Jurasz, Paul; Alonso-Escolano, David; Drews, Magdalena; Morandi, Maria; Malinski, Tadeusz; Radomski, Marek W

    2005-11-01

    Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.

  15. Tissue Inhibitor of Metalloproteinase 1 Influences Vascular Adaptations to Chronic Alterations in Blood Flow.

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    Mandel, Erin R; Uchida, Cassandra; Nwadozi, Emmanuel; Makki, Armin; Haas, Tara L

    2017-04-01

    Remodeling of the skeletal muscle microvasculature involves the coordinated actions of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitor of metalloproteinases (TIMPs). We hypothesized that the loss of TIMP1 would enhance both ischemia and flow-induced vascular remodeling by increasing MMP activity. TIMP1 deficient (Timp1(-/-) ) and wild-type (WT) C57BL/6 mice underwent unilateral femoral artery (FA) ligation or were treated with prazosin, an alpha-1 adrenergic receptor antagonist, in order to investigate vascular remodeling to altered flow. Under basal conditions, Timp1(-/-) mice had reduced microvascular content as compared to WT mice. Furthermore, vascular remodeling was impaired in Timp1(-/-) mice. Timp1(-/-) mice displayed reduced blood flow recovery in response to FA ligation and no arteriogenic response to prazosin treatment. Timp1(-/-) mice failed to undergo angiogenesis in response to ischemia or prazosin, despite maintaining the capacity to increase VEGF-A and eNOS mRNA. Vascular permeability was increased in muscles of Timp1(-/-) mice in response to both prazosin treatment and FA ligation, but this was not accompanied by greater MMP activity. This study highlights a previously undescribed integral role for TIMP1 in both vascular network maturation and adaptations to ischemia or alterations in flow. J. Cell. Physiol. 232: 831-841, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Quantification of blood flow and topology in developing vascular networks.

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    Astrid Kloosterman

    Full Text Available Since fluid dynamics plays a critical role in vascular remodeling, quantification of the hemodynamics is crucial to gain more insight into this complex process. Better understanding of vascular development can improve prediction of the process, and may eventually even be used to influence the vascular structure. In this study, a methodology to quantify hemodynamics and network structure of developing vascular networks is described. The hemodynamic parameters and topology are derived from detailed local blood flow velocities, obtained by in vivo micro-PIV measurements. The use of such detailed flow measurements is shown to be essential, as blood vessels with a similar diameter can have a large variation in flow rate. Measurements are performed in the yolk sacs of seven chicken embryos at two developmental stages between HH 13+ and 17+. A large range of flow velocities (1 µm/s to 1 mm/s is measured in blood vessels with diameters in the range of 25-500 µm. The quality of the data sets is investigated by verifying the flow balances in the branching points. This shows that the quality of the data sets of the seven embryos is comparable for all stages observed, and the data is suitable for further analysis with known accuracy. When comparing two subsequently characterized networks of the same embryo, vascular remodeling is observed in all seven networks. However, the character of remodeling in the seven embryos differs and can be non-intuitive, which confirms the necessity of quantification. To illustrate the potential of the data, we present a preliminary quantitative study of key network topology parameters and we compare these with theoretical design rules.

  17. Blood flow controls bone vascular function and osteogenesis

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    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  18. Surveillance of hemodialysis vascular access with ultrasound vector flow imaging

    Science.gov (United States)

    Brandt, Andreas H.; Olesen, Jacob B.; Hansen, Kristoffer L.; Rix, Marianne; Jensen, Jørgen A.; Nielsen, Michael B.

    2015-03-01

    The aim of this study was prospectively to monitor the volume flow in patients with arteriovenous fistula (AVF) with the angle independent ultrasound technique Vector Flow Imaging (VFI). Volume flow values were compared with Ultrasound dilution technique (UDT). Hemodialysis patients need a well-functioning vascular access with as few complications as possible and preferred vascular access is an AVF. Dysfunction due to stenosis is a common complication, and regular monitoring of volume flow is recommended to preserve AVF patency. UDT is considered the gold standard for volume flow surveillance, but VFI has proven to be more precise, when performing single repeated instantaneous measurements. Three patients with AVF were monitored with UDT and VFI monthly for five months. A commercial ultrasound scanner with a 9 MHz linear array transducer with integrated VFI was used to obtain data. UDT values were obtained with Transonic HD03 Flow-QC Hemodialysis Monitor. Three independent measurements at each scan session were obtained with UDT and VFI each month. Average deviation of volume flow between UDT and VFI was 25.7 % (Cl: 16.7% to 34.7%) (p= 0.73). The standard deviation for all patients, calculated from the mean variance of each individual scan sessions, was 199.8 ml/min for UDT and 47.6 ml/min for VFI (p = 0.002). VFI volume flow values were not significantly different from the corresponding estimates obtained using UDT, and VFI measurements were more precise than UDT. The study indicates that VFI can be used for surveillance of volume flow.

  19. Angiopoietin-2 is critical for cytokine-induced vascular leakage.

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    Andrew V Benest

    Full Text Available Genetic experiments (loss-of-function and gain-of-function have established the role of Angiopoietin/Tie ligand/receptor tyrosine kinase system as a regulator of vessel maturation and quiescence. Angiopoietin-2 (Ang-2 acts on Tie2-expressing resting endothelial cells as an antagonistic ligand to negatively interfere with the vessel stabilizing effects of constitutive Ang-1/Tie-2 signaling. Ang-2 thereby controls the vascular response to inflammation-inducing as well as angiogenesis-inducing cytokines. This study was aimed at assessing the role of Ang-2 as an autocrine (i.e. endothelial-derived regulator of rapid vascular responses (within minutes caused by permeability-inducing agents. Employing two independent in vivo assays to quantitatively assess vascular leakage (tracheal microsphere assay, 1-5 min and Miles assay, 20 min, the immediate vascular response to histamine, bradykinin and VEGF was analyzed in Ang-2-deficient (Ang-2(-/- mice. In comparison to the wild type control mice, the Ang2(-/- mice demonstrated a significantly attenuated response. The Ang-2(-/- phenotype was rescued by systemic administration (paracrine of an adenovirus encoding Ang-2. Furthermore, cytokine-induced intracellular calcium influx was impaired in Ang-2(-/- endothelioma cells, consistent with reduced phospholipase activation in vivo. Additionally, recombinant human Ang-2 (rhAng-2 alone was unable to induce vascular leakage. In summary, we report here in a definite genetic setting that Ang-2 is critical for multiple vascular permeability-inducing cytokines.

  20. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond.

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    Di Lisi, Daniela; Madonna, Rosalinda; Zito, Concetta; Bronte, Enrico; Badalamenti, Giuseppe; Parrella, Paolo; Monte, Ines; Tocchetti, Carlo Gabriele; Russo, Antonio; Novo, Giuseppina

    2017-01-15

    Cardiotoxicity induced by chemotherapeutic agents and radiotherapy is a growing problem. In recent years, an increasing number of new drugs with targeted action have been designed. These molecules, such as monoclonal antibodies and tyrosine kinase inhibitors, can cause different type of toxicities compared to traditional chemotherapy. However, they can also cause cardiac complications such as heart failure, arterial hypertension, QT interval prolongation and arrhythmias. Currently, a field of intense research is the vascular toxicity induced by new biologic drugs, particularly those which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and other tyrosine kinases. In this review, we aim at focusing on the problem of vascular toxicity induced by new targeted therapies, chemotherapy and radiotherapy, and describe the main mechanisms and emphasizing the importance of early diagnosis of vascular damage, in order to prevent clinical complications.

  1. Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation.

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    Iván eRodríguez

    2014-09-01

    Full Text Available Physiological vascular function regulation is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the main risk factors of cardiovascular pathology, where the imbalance between the synthesis of vasodilator and vasoconstrictor molecules is common in the development of vascular disorders in systemic and placental circulation. In the placenta, an organ without autonomic innervations, the local control of vascular tone is critical for maintenance of fetal growth and mechanisms that underlie shear stress response induced by blood flow are essential during pregnancy. In this field, shear stress induced by moderate exercise is one of the most important mechanisms to improve vascular function through nitric oxide (NO synthesis and stimulation of mechanical response of endothelial cells triggered by ion channels, caveolae, endothelial NO synthase (eNOS and vascular endothelial growth factor (VEGF, among others. The demand for oxygen and nutrients by tissues and organs, especially in placentation and pregnancy, determines blood flow parameters and physiological adaptations of vascular beds for covering metabolic requirements. In this regard, moderate exercise versus sedentarism shows potential benefits for improving vascular function associated with the enhancement of molecular mechanisms induced by shear stress. In this review, we collect evidence about molecular bases of physiological response to shear stress in order to highlight the relevance of moderate exercise-training for vascular health in adult and fetal life.

  2. Effects of hypothyroidism on vascular /sup 125/I-albumin permeation and blood flow in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, R.G.; Pugliese, G.; Chang, K.; Speedy, A.; Province, M.A.; Kilo, C.; Williamson, J.R.

    1989-05-01

    Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern was observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.

  3. Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy.

    Science.gov (United States)

    Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B

    2016-02-01

    Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5-1 ml·g(-1)·min(-1) and increased to 2-3 ml·g(-1)·min(-1) with catecholamine infusion and to ∼4 ml·g(-1)·min(-1) with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1-0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, "tracking" closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states.

  4. Interaction between human monocytes and vascular smooth muscle cells induces vascular endothelial growth factor expression.

    Science.gov (United States)

    Hojo, Y; Ikeda, U; Maeda, Y; Takahashi, M; Takizawa, T; Okada, M; Funayama, H; Shimada, K

    2000-05-01

    The objective of this study was to investigate whether synthesis of vascular endothelial growth factor (VEGF), a major mitogen for vascular endothelial cells, was induced by a cell-to-cell interaction between monocytes and vascular smooth muscle cells (VSMCs). Human VSMCs and THP-1 cells (human monocytoid cell) were cocultured. VEGF levels in the coculture medium were determined by enzyme-linked immunosorbent assay. Northern blot analysis of VEGF mRNA was performed using a specific cDNA probe. Immunohistochemistry was performed to determine which types of cell produce VEGF. Adding THP-1 cells to VSMCs for 24 h increased VEGF levels of the culture media, 8- and 10-fold relative to those of THP-1 cells and VSMCs alone, respectively. Northern blot analysis showed that VEGF mRNA expression was induced in the cocultured cells and peaked after 12 h. Immunohistochemistry disclosed that both types of cell in the coculture produced VEGF. Separate coculture experiments revealed that both direct contact and a soluble factor(s) contributed to VEGF production. Neutralizing anti-interleukin (IL)-6 antibody inhibited VEGF production by the coculture of THP-1 cells and VSMCs. A cell-to-cell interaction between monocytes and VSMCs induced VEGF synthesis in both types of cell. An IL-6 mediated mechanism is at least partially involved in VEGF production by the cocultures. Local VEGF production induced by a monocyte-VSMC interaction may play an important role in atherosclerosis and vascular remodeling.

  5. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    Science.gov (United States)

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

  6. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  7. Drinking citrus fruit juice inhibits vascular remodeling in cuff-induced vascular injury mouse model.

    Science.gov (United States)

    Ohnishi, Arika; Asayama, Rie; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Horiuchi, Masatsugu

    2015-01-01

    Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI.

  8. Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

    Science.gov (United States)

    Tarapacki, Christine; Kuebler, Wolfgang M.; Tabuchi, Arata; Karshafian, Raffi

    2017-03-01

    Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 µL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular

  9. Focused ultrasound surgery-induced vascular occlusion in fetal medicine

    Science.gov (United States)

    Rivens, Ian H.; Rowland, Ian; Denbow, Mark; Fisk, Nicholas M.; Leach, Martin O.; ter Haar, Gail R.

    1998-04-01

    Aim: This study investigates whether it is possible to occlude blood flow in vivo using high intensity focused ultrasound surgery (FUS). Such an effect could be used in the non-invasive treatment of fetal dysfunctions. Conclusion: Our ability to curtail blood flow using FUS allows the possibility of non-invasively treating feto-fetal transfusion syndrome by occluding the placental shunt vessels responsible for the vascular imbalance in twins sharing a placenta. This would have advantages over currently available interventional treatments (surgery or intrauterine lasers), which have significant related mortality and morbidity.

  10. Fibro-vascular coupling in the control of cochlear blood flow.

    Directory of Open Access Journals (Sweden)

    Min Dai

    Full Text Available BACKGROUND: Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained. METHODOLOGY/PRINCIPAL FINDINGS: We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca(2+ signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca(2+ sensor, fluo-4. Elevation of Ca(2+ in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca(2+ signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF. Cyclooxygenase-1 (COX-1 was required for capillary dilation. CONCLUSIONS/SIGNIFICANCE: The findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity.

  11. Management of Low-Flow Vascular Malformations: Clinical Presentation, Classification, Patient Selection, Imaging and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    McCafferty, Ian, E-mail: ian.mccafferty@uhb.nhs.uk [Queen Elizabeth Hospital Birmingham (QEHB) & Birmingham Children’s Hospital (BCH) (United Kingdom)

    2015-10-15

    This review article aims to give an overview of the current state of imaging, patient selection, agents and techniques used in the management of low-flow vascular malformations. The review includes the current classifications for low-flow vascular malformations including the 2014 updates. Clinical presentation and assessment is covered with a detailed section on the common sclerosant agents used to treat low-flow vascular malformations, including dosing and common complications. Imaging is described with a guide to a simple stratification of the use of imaging for diagnosis and interventional techniques.

  12. Eicosanoid signaling and vascular dysfunction: methylmercury-induced phospholipase D activation in vascular endothelial cells.

    Science.gov (United States)

    Sherwani, Shariq I; Pabon, Sheila; Patel, Rishi B; Sayyid, Muzzammil M; Hagele, Thomas; Kotha, Sainath R; Magalang, Ulysses J; Maddipati, Krishna R; Parinandi, Narasimham L

    2013-11-01

    Mercury, especially methylmercury (MeHg), is implicated in the etiology of cardiovascular diseases. Earlier, we have reported that MeHg induces phospholipase D (PLD) activation through oxidative stress and thiol-redox alteration. Hence, we investigated the mechanism of the MeHg-induced PLD activation through the upstream regulation by phospholipase A2 (PLA2) and lipid oxygenases such as cyclooxygenase (COX) and lipoxygenase (LOX) in the bovine pulmonary artery endothelial cells (BPAECs). Our results showed that MeHg significantly activated both PLA2 (release of [(3)H]arachidonic acid, AA) and PLD (formation of [(32)P]phosphatidylbutanol) in BPAECs in dose- (0-10 μM) and time-dependent (0-60 min) fashion. The cPLA2-specific inhibitor, arachidonyl trifluoromethyl ketone (AACOCF3), significantly attenuated the MeHg-induced [(3)H]AA release in ECs. MeHg-induced PLD activation was also inhibited by AACOCF3 and the COX- and LOX-specific inhibitors. MeHg also induced the formation of COX- and LOX-catalyzed eicosanoids in ECs. MeHg-induced cytotoxicity (based on lactate dehydrogenase release) was protected by PLA2-, COX-, and LOX-specific inhibitors and 1-butanol, the PLD-generated PA quencher. For the first time, our studies showed that MeHg activated PLD in vascular ECs through the upstream action of cPLA2 and the COX- and LOX-generated eicosanoids. These results offered insights into the mechanism(s) of the MeHg-mediated vascular endothelial cell lipid signaling as an underlying cause of mercury-induced cardiovascular diseases.

  13. Lanthanum prevents high phosphate-induced vascular calcification by preserving vascular smooth muscle lineage markers.

    Science.gov (United States)

    Ciceri, Paola; Elli, Francesca; Brenna, Irene; Volpi, Elisa; Romagnoli, Solange; Tosi, Delfina; Braidotti, Paola; Brancaccio, Diego; Cozzolino, Mario

    2013-06-01

    Vascular calcification (VC) represents a major cardiovascular risk factor in chronic kidney disease patients. High phosphate (Pi) levels are strongly associated with VC in this population. Therefore, Pi binders are commonly used to control high Pi levels. The aim of this work was to study the mechanism of action of lanthanum chloride (LaCl3) on the progression of Pi-induced VC through its direct effect on vascular smooth muscle cells (VSMCs) in vitro. High Pi induced VSCM Ca deposition. We evaluated the action of LaCl3, compared to gadolinium chloride (GdCl3), and found different effects on the modulation of VSMC lineage markers, such as α-actin and SM22α. In fact, only LaCl3 preserved the expression of both VSMC lineage markers compared to high Pi-treated cells. Interestingly, both LaCl3 and GdCl3 reduced the high Pi-induced elevations of bone morphogenic protein 2 mRNA expression, with no reduction of the high core binding factor-alpha 1 mRNA levels observed in calcified VSMCs. Furthermore, we also found that only LaCl3 completely prevented the matrix GLA protein mRNA levels and osteonectin protein expression elevations induced by high Pi compared to GdCl3. Finally, LaCl3, in contrast to GdCl3, prevented the high Pi-induced downregulation of Axl, a membrane tyrosine kinase receptor involved in apoptosis. Thus, our results suggest that LaCl3 prevents VC by preserving VSMC lineage markers and by decreasing high Pi-induced osteoblastic differentiation.

  14. EFFECTS OF VASCULAR ZERO-STRESS STATE ON PULSATILE BLOOD FLOW

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, blood flow in artery was treated as the flow under equilibrium state (the steady flow under mean pressure) combined with the periodically small pulsatile flow. Based on vascular zero-stress state[1], the pulsatile strains according to the radial and axial displacements of blood vessel were obtained. With the use of Hooke’s law, the pulsatile strains and the corresponding Cauchy stresses were connected, so the corresponding wall motion equations could be established here. By solving the linearized Navier-Stokes equations, the analytic expressions of the blood flow velocities and the vascular displacements could be obtained, and the influence of the circumferential and axial stretch ratio on pulsatile blood flow and vascular motion was discussed in details.

  15. Physiological and Therapeutic Vascular Remodeling Mediated by Hypoxia-Inducible Factor 1

    Science.gov (United States)

    Sarkar, Kakali; Semenza, Gregg L.

    Angiogenesis along with arteriogenesis and vasculogenesis is a fundamental process in ischemic repair in adult animals including humans. Hypoxia-inducible factor 1 (HIF-1) plays a central role in mediating adaptive responses to hypoxia/ischemia by expressing angiogenic cytokines/growth factors and their cognate receptors. Angiogenic growth factors are the homing signal for circulating angiogenic cells (CACs), which are mobilized to peripheral blood from bone marrow, recruited to target tissues, and promote vascularization. Impairment of HIF-1-mediated gene transcription contributes to the impaired vascular responses in peripheral vascular disease that are associated with aging and diabetes. Promoting neovascularization in ischemic tissues is a promising strategy for the treatment of peripheral vascular disease when surgical or catheter-based revascularization is not possible. Intramuscular injection of an adenovirus encoding a constitutively active form of HIF-1α (AdCA5), into the ischemic limb of diabetic mice increases the recovery of limb perfusion and function, rescues the diabetes-associated impairment of CACs, and increases vascularization. Administration of AdCA5 overcomes the effect of aging on recovery of blood flow in middle-aged mice following femoral artery ligation in a mouse model of age-dependent critical limb ischemia. Intramuscular injection of AdCA5 along with intravenous injection of bone-marrow-derived angiogenic cells cultured in the presence of prolyl-4-hydroxylase inhibitor dimethyloxalylglycine, increases blood flow and limb salvage in old mice following femoral artery ligation. HIF-1α gene therapy increases homing of bone-marrow-derived cells, whereas induction of HIF-1 in these cells increases their retention in the ischemic tissue by increasing their adhesion to endothelium leading to synergistic effects of combined therapy on improving blood flow.

  16. Additive effect of red blood cell rigidity and adherence to endothelial cells in inducing vascular resistance.

    Science.gov (United States)

    Kaul, D K; Koshkaryev, A; Artmann, G; Barshtein, G; Yedgar, S

    2008-10-01

    To explore the contribution of red blood cell (RBC) deformability and interaction with endothelial cells (ECs) to circulatory disorders, these RBC properties were modified by treatment with hydrogen peroxide (H(2)O(2)), and their effects on vascular resistance were monitored following their infusion into rat mesocecum vasculature. Treatment with 0.5 mM H(2)O(2) increased RBC/EC adherence without significant alteration of RBC deformability. At 5.0 mM H(2)O(2), RBC deformability was considerably reduced, inducing a threefold increase in the number of undeformable cells, whereas RBC/EC adherence was not further affected by the increased H(2)O(2) concentration. This enabled the selective manipulation of RBC adherence and deformability and the testing of their differential effect on vascular resistance. Perfusion of RBCs with enhanced adherence and unchanged deformability (treatment with 0.5 mM H(2)O(2)) increased vascular resistance by about 35% compared with untreated control RBCs. Perfusion of 5.0 mM H(2)O(2)-treated RBCs, with reduced deformability (without additional increase of adherence), further increased vascular resistance by about 60% compared with untreated control RBCs. These results demonstrate the specific effects of elevated adherence and reduced deformability of oxidized RBCs on vascular resistance. These effects can be additive, depending on the oxidation conditions. The oxidation-induced changes applied in this study are moderate compared with those observed in RBCs in pathological states. Yet, they caused a considerable increase in vascular resistance, thus demonstrating the potency of RBC/EC adherence and RBC deformability in determining resistance to blood flow in vivo.

  17. New Insights Into Tobacco-Induced Vascular Disease: Clinical Ramifications.

    Science.gov (United States)

    Cooke, John P

    2015-01-01

    Tobacco smoke contains more than 4,000 compounds. These include phenols, carbonyls, and nitrosamines that may be irritants and carcinogens; particulate matter such as tars; volatiles and gases such as carbon monoxide; and nicotine. Many of these compounds may contribute to the adverse health effects of tobacco. For example, recent findings have shown that the angiogenic and proliferative effects of nicotine are mediated by activation of nicotinic receptors on the vascular cells. Nicotine-induced activation of vascular cells may contribute to pathological neovascularization in cancer, age-related macular degeneration, and atherosclerosis. This review focuses on how nicotine adversely affects cardiovascular health and highlights intriguing new data about nicotine's potent angiogenic and proliferative properties.

  18. Betahistine-induced vascular effects in the rat cochlea.

    Science.gov (United States)

    Laurikainen, E A; Miller, J M; Quirk, W S; Kallinen, J; Ren, T; Nuttall, A L; Grénman, R; Virolainen, E

    1993-01-01

    Betahistine (BH) has been used widely to treat cochlear disorders, such as tinnitus and Meniere's disease. The mechanism of action of BH in the cochlea is assumed to be based on its histamine-like effect on H1 receptors in the cochlear vasculature, leading to an increased cochlear blood flow (CBF). Recently it has been shown that BH can strongly affect H3 heteroreceptors (a novel histamine receptor subclass) in the periphery, via an autonomic ligand. This mechanism may also contribute to the BH effects on CBF. This study was to validate BH effects in the cochlear vasculature and to investigate the possible mechanisms of action of this drug in the inner ear vasculature. We assessed the effects of BH on CBF with the laser Doppler flowmeter in 23 rats and concluded that BH affects vascular conductivity in the cochlea in a dose-dependent fashion; betahistine diffuses through the round window, but does not have access to vascular receptors or ligands once in the labyrinthine fluids; and the H1 receptors mediate the systemic and peripheral vascular effects of BH, whereas the cochlear effect involves cholinergic receptors.

  19. Eccentric-exercise induced inflammation attenuates the vascular responses to mental stress.

    Science.gov (United States)

    Paine, Nicola J; Ring, Christopher; Aldred, Sarah; Bosch, Jos A; Wadley, Alex J; Veldhuijzen van Zanten, Jet J C S

    2013-05-01

    Mental stress has been identified as a trigger of myocardial infarction (MI), with inflammation and vascular responses to mental stress independently implicated as contributing factors. This study examined whether inflammation moderates the vascular responses to mental stress. Eighteen healthy male participants completed a stress task under two counter balanced conditions. In the exercise condition, a morning bout of eccentric exercise (12×5 repetitions of unilateral eccentric knee extension at 120% intensity of concentric one repetition maximum) was used to increase levels of inflammatory-responsive cytokines during an afternoon stress session scheduled 6h later. In the control condition, participants sat and relaxed for 45min, 6h prior to the afternoon stress session. Forearm blood flow, calf blood flow (measured in the leg which completed the exercise task), blood pressure, heart rate and cardiac output were assessed at rest and in response to mental stress. As expected, interleukin-6 was higher (p=.02) 6h post exercise, i.e., at the start of the stress session, as compared to the no-exercise control condition. Mental stress increased forearm blood flow, calf blood flow, blood pressure, heart rate, and cardiac output in both conditions (p'sexercise condition compared to the control condition (peccentric exercise attenuated the vascular responses to mental stress locally at the site of eccentric exercise-induced inflammation. The observed impairment in vascular responses to stress associated with increased levels of inflammation suggests a mechanism through which inflammation might increase the risk for MI. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    NARCIS (Netherlands)

    Drongelen, J. van; Koppen, A. van; Pertijs, J.C.L.M.; Gooi, J.H.; Parry, L.J.; Sweep, F.C.; Lotgering, F.K.; Smits, P.; Spaanderman, M.E.A.

    2012-01-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a re

  1. EFFECT OF ELECTROACUPUNCTURE ON CEREBRAL BLOOD FLOW,VIP AND ET IN RATS WITH VASCULAR DEMENTIA

    Institute of Scientific and Technical Information of China (English)

    申国明; 徐颖; 何峰; 许冠荪

    2004-01-01

    Objective: To investigate the relationship between electroacupuncture (EA)-induced improvement of regional cerebral blood flow and the alternations of vasoactive intestinal peptide (VIP) and endothelin (ET) in rats with experimental vascular dementia (VD).Methods: 40 Wistar rats were evenly randomized into sham-operation, model, medication (Nimotone) and EA groups.Vascular dementia model was established by repeated cerebral ischemia-reperfusion which was induced by occlusion and reopen of the bilateral common carotid arteries.EA (2~200 Hz, 2~3 mA) was applied to "Baihui"(GV 20), "Dazhui"(GV 14) and "Zusanli"(ST 36) for 30 min, once daily and continuously for 15 days.The regional cerebral blood flow (rCBF) in parietal lobe and hippocampus was determined with method of hydrogen clearance; a step-down avoidance test was adopted to observe the rats' behavior change; and plasma VIP and ET contents were assayed by radioimmunoassay.Results: In comparison with sham-operation group, the correct rate of step-down avoidance test, rCBF in parietal lobe and hippocampus and plasma VIP level in VD model group lowered significantly (P<0.01) and plasma ET increased considerably (P<0.01).However, compared with model group, the correct rate of step-down avoidance test, rCBF values and plasma VIP in EA group raised obviously while plasma ET declined significantly.No significant differences were found between EA and medication groups in the 4 indexes.Conclusion: EA can raise rCBF in the parietal lobe and hippocampus, elevate plasma VIP level and reduce plasma ET in rats with VD.

  2. VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shang; Dang, Yuan Ye; Oi Lam Che, Ginny [State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao (China); Kwan, Yiu Wa [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China); Chan, Shun Wan [State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong (China); Leung, George Pak Heng [Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong (China); Lee, Simon Ming Yuen, E-mail: simonlee@umac.mo [State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao (China); Hoi, Maggie Pui Man, E-mail: maghoi@umac.mo [State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao (China)

    2014-11-01

    In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways.

  3. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension

    Science.gov (United States)

    Phan, Carole; Seferian, Andrei; Huertas, Alice; Thuillet, Raphaël; Sattler, Caroline; Le Hiress, Morane; Tamura, Yuichi; Jutant, Etienne-Marie; Chaumais, Marie-Camille; Bouchet, Stéphane; Manéglier, Benjamin; Molimard, Mathieu; Rousselot, Philippe; Sitbon, Olivier; Simonneau, Gérald; Montani, David; Humbert, Marc

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, a dual Src and BCR-ABL tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in the long-term development of dasatinib-induced PAH. Here, we demonstrated that chronic dasatinib therapy causes pulmonary endothelial damage in humans and rodents. We found that dasatinib treatment attenuated hypoxic pulmonary vasoconstriction responses and increased susceptibility to experimental pulmonary hypertension (PH) in rats, but these effects were absent in rats treated with imatinib, another BCR-ABL tyrosine kinase inhibitor. Furthermore, dasatinib treatment induced pulmonary endothelial cell apoptosis in a dose-dependent manner, while imatinib did not. Dasatinib treatment mediated endothelial cell dysfunction via increased production of ROS that was independent of Src family kinases. Consistent with these findings, we observed elevations in markers of endothelial dysfunction and vascular damage in the serum of CML patients who were treated with dasatinib, compared with CML patients treated with imatinib. Taken together, our findings indicate that dasatinib causes pulmonary vascular damage, induction of ER stress, and mitochondrial ROS production, which leads to increased susceptibility to PH development. PMID:27482885

  4. RO-heparin Inhibits L-Selectin-mediated Neutrophils Adhesion to Vascular Endothelium Under Flow Conditions

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin's anti-inflammatory effects are mainly mediated by blocking L- or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydridereduced heparin (RO-heparin) can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte rolling on thioglycollate-induced rat mesenteric venules and L-selectin-metadiated neutrophil rolling on TNF-α-induced human umbilical vein endothelial cells(HUVECs) under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.

  5. Surveillance of Hemodialysis Vascular Access with Ultrasound Vector Flow Imaging

    DEFF Research Database (Denmark)

    Brandt, Andreas Hjelm; Olesen, Jacob Bjerring; Lindskov Hansen, Kristoffer;

    2015-01-01

    The aim of this study was prospectively to monitor the volume flow in patients with arteriovenous fistula (AVF) with the angle independent ultrasound technique Vector Flow Imaging (VFI). Volume flow values were compared with Ultrasound dilution technique (UDT). Hemodialysis patients need a well...... obtained with Transonic HD03 Flow-QC Hemodialysis Monitor. Three independent measurements at each scan session were obtained with UDT and VFI each month. Average deviation of volume flow between UDT and VFI was 25.7 % (Cl: 16.7% to 34.7%) (p= 0.73). The standard deviation for all patients, calculated from...

  6. Flow-dependent regulation of vascular function and gene expression in rat superior mesenteric artery

    Institute of Scientific and Technical Information of China (English)

    XIA Shang; DENG Chang-sheng

    2009-01-01

    Background Mesenteric artery thrombosis is prone to occur at specific arterial regions with different fluid flow patterns,yet mechanistic links between blood flow and vascular function remain unclear. This study aired to investigate the role of blood flow in regulation of vascular function and gene expression in rats.Methods Isometric tension was recorded in wire myograph to examine vascular function of specific regions (trunk parts and proximal parts from the origin) with different blood flow in superior mesenteric artery (SMA). Endothelial nitric oxide syntheses (eNOS), phosphorylated-eNOS (p-eNOS), serine-threonine kinase Akt and phosphorylated-Akt (p-Akt) protein expressions in SMA were examined by Western blotting. Significance was analyzed using a Student's ttest or analysis of variance (ANOVA) followed by a Dunnett's multiple-comparison post hoc test.Results Compared with trunks, proximal parts exhibited severely impaired relaxant responses to acetylcholine (Ach) (1 nmol/L to 10 pmol/L) (P 0.05).Conclusion Critical components that drive the vascular function and influence the localization of mesenteric artery thrombosis are flow-responsive elements within the vascular endothelium.

  7. The contribution of vascular and extra-vascular water pathways to drought-induced decline of leaf hydraulic conductance.

    Science.gov (United States)

    Trifiló, Patrizia; Raimondo, Fabio; Savi, Tadeja; Lo Gullo, Maria A; Nardini, Andrea

    2016-09-01

    Drought stress can impair leaf hydraulic conductance (Kleaf), but the relative contribution of changes in the efficiency of the vein xylem water pathway and in the mesophyll route outside the xylem in driving the decline of Kleaf is still debated. We report direct measurements of dehydration-induced changes in the hydraulic resistance (R=1/K) of whole leaf (Rleaf), as well as of the leaf xylem (Rx) and extra-vascular pathways (Rox) in four Angiosperm species. Rleaf, Rx, and Rox were measured using the vacuum chamber method (VCM). Rleaf values during progressive leaf dehydration were also validated with measurements performed using the rehydration kinetic method (RKM). We analysed correlations between changes in Rx or Rox and Rleaf, as well as between morpho-anatomical traits (including dehydration-induced leaf shrinkage), vulnerability to embolism, and leaf water relation parameters. Measurements revealed that the relative contribution of vascular and extra-vascular hydraulic properties in driving Kleaf decline during dehydration is species-specific. Whilst in two study species the progressive impairment of both vascular and extra-vascular pathways contributed to leaf hydraulic vulnerability, in the other two species the vascular pathway remained substantially unaltered during leaf dehydration, and Kleaf decline was apparently caused only by changes in the hydraulic properties of the extra-vascular compartment.

  8. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an impo

  9. High-flow vascular malformation treatment using ultrasound-guided laser combined with polidocanol sclerotherapy.

    Science.gov (United States)

    Zhang, Yan; Zhou, Ping; Li, Lan; Li, Jia-le

    2015-07-01

    The current treatment for vascular malformations includes surgery, sclerotherapy, and embolization. However, each method has its limitations, such as recurrence, complications, scarring, and radiation exposure. Therefore, identifying an effective, minimally invasive treatment that reduces lesion recurrence is particularly important. We describe in detail a patient who received treatment with ultrasound-guided laser interruption of feeding vessels combined with polidocanol sclerotherapy after the recurrence of forearm high-flow vascular malformation.

  10. Correlation between penile cavernosal artery blood flow and retinal vascular findings in arteriogenic erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Ahmed M Emarah

    2010-09-01

    Full Text Available Ahmed M Emarah1, Shawky M El-Haggar2, Ihab A Osman2, Abdel Wahab S Khafagy21Departments of Ophthalmology, 2Andrology and Sexology, Cairo University Hospital, EgyptObjectives: Arteriogenic erectile dysfunction (ED is a target organ disease of atherosclerosis, and therefore might be a predictor of systemic atherosclerosis. Being systemic, it might be possible to evaluate the extent of atherosclerosis from retinal vascular findings. We investigated the possible correlation between penile cavernosal artery blood flow and retinal vascular findings in patients with arteriogenic ED.Patients and methods: Sixty patients with ED were divided according to the peak systolic velocity (PSV in their penile cavernosal arteries into two groups; Group A included 30 patients with PSV less than 25 cm/sec, and Group B included 30 patients with PSV more than 35 cm/sec. Blood flow in the penile cavernosal artery was measured with color Doppler ultrasonography. All patients were assessed by ocular fundus examination under amydriatic conditions to evaluate retinal vascular atherosclerotic changes using Hyman’s classification.Results: Evidence of retinal vascular atherosclerotic changes was found in 19 patients (63.3% in Group A and in 10 patients (33.3% in Group B.Conclusions: Our study confirms the possibility of predicting penile arterial vascular status in patients with ED from their retinal vascular findings by using amydriatic simple, practical funduscopy.Keywords: erectile dysfunction, atherosclerosis, retinal vascular atherosclerosis

  11. Blood flow measurements during hemodialysis vascular access interventions - Catheter-based thermodilution or Doppler ultrasound?

    DEFF Research Database (Denmark)

    Heerwagen, Søren T; Hansen, Marc A; Schroeder, Torben V

    2012-01-01

    Purpose: To test the clinical performance of catheter-based thermodilution and Doppler ultrasound of the feeding brachial artery for blood flow measurements during hemodialysis vascular access interventions.Methods: Thirty patients with arteriovenous fistulas who underwent 46 interventions had...... access blood flow measured before and after every procedure. Two methods, catheter-based thermodilution and Doppler ultrasound, were compared to the reference method of ultrasound dilution. Catheter-based thermodilution and Doppler ultrasound were performed during the endovascular procedures while flow...

  12. Different contributions of clathrin- and caveolae-mediated endocytosis of vascular endothelial cadherin to lipopolysaccharide-induced vascular hyperpermeability.

    Science.gov (United States)

    Zhang, Ye; Zhang, Lianyang; Li, Yang; Sun, Shijin; Tan, Hao

    2014-01-01

    Vascular hyperpermeability induced by lipopolysaccharide (LPS) is a common pathogenic process in cases of severe trauma and sepsis. Vascular endothelial cadherin (VE-cad) is a key regulatory molecule involved in this process, although the detailed mechanism through which this molecule acts remains unclear. We assessed the role of clathrin-mediated and caveolae-mediated endocytosis of VE-cad in LPS-induced vascular hyperpermeability in the human vascular endothelial cell line CRL-2922 and determined that vascular permeability and VE-cad localization at the plasma membrane were negatively correlated after LPS treatment. Additionally, the loss of VE-cad at the plasma membrane was caused by both clathrin-mediated and caveolae-mediated endocytosis. Clathrin-mediated endocytosis was dominant early after LPS treatment, and caveolae-mediated endocytosis was dominant hours after LPS treatment. The caveolae-mediated endocytosis of VE-cad was activated through the LPS-Toll-like receptor 4 (TLR4)-Src signaling pathway. Structural changes in the actin cytoskeleton, specifically from polymerization to depolymerization, were important reasons for the switching of the VE-cad endocytosis pathway from clathrin-mediated to caveolae-mediated. Our findings suggest that clathrin-mediated and caveolae-mediated endocytosis of VE-cad contribute to LPS-induced vascular hyperpermeability, although they contribute via different mechanism. The predominant means of endocytosis depends on the time since LPS treatment.

  13. Vaccine-induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    N.J. Paine; C. Ring; J.A. Bosch; M.T. Drayson; S. Aldred; J.J.C.S. Veldhuijzen van Zanten

    2014-01-01

    Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male

  14. Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

    Science.gov (United States)

    Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

    2017-01-01

    Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min(-1)·mmHg(-1), respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min(-1)·mmHg(-1), respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically.

  15. Interactive effects of vascular risk burden and advanced age on cerebral blood flow

    Directory of Open Access Journals (Sweden)

    Katherine eBangen

    2014-07-01

    Full Text Available Vascular risk factors and cerebral blood flow (CBF reduction have been linked to increased risk of cognitive impairment and Alzheimer’s disease (AD; however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors, advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor. This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus, inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus, and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines.

  16. Quantitative analysis of cytokine-induced vascular toxicity and vascular leak in the mouse brain.

    Science.gov (United States)

    Irwan, Yetty Y; Feng, Yi; Gach, H Michael; Symanowski, James T; McGregor, John R; Veni, Gopalkrishna; Schabel, Matthias; Samlowski, Wolfram E

    2009-09-30

    A storm of inflammatory cytokines is released during treatment with pro-inflammatory cytokines, such as interleukin-2 (IL-2), closely approximating changes initially observed during sepsis. These signals induce profound changes in neurologic function and cognition. Little is known about the mechanisms involved. We evaluated a number of experimental methods to quantify changes in brain blood vessel integrity in a well-characterized IL-2 treatment mouse model. Measurement of wet versus dry weight and direct measurement of small molecule accumulation (e.g. [(3)H]-H(2)O, sodium fluorescein) were not sensitive or reliable enough to detect small changes in mouse brain vascular permeability. Estimation of brain water content using proton density magnetic resonance imaging (MRI) measurements using a 7T mouse MRI system was sensitive to 1-2% changes in brain water content, but was difficult to reproduce in replicate experiments. Successful techniques included use of immunohistochemistry using specific endothelial markers to identify vasodilation in carefully matched regions of brain parenchyma and dynamic contrast enhanced (DCE) MRI. Both techniques indicated that IL-2 treatment induced vasodilation of the brain blood vessels. DCE MRI further showed a 2-fold increase in the brain blood vessel permeability to gadolinium in IL-2 treated mice compared to controls. Both immunohistochemistry and DCE MRI data suggested that IL-2 induced toxicity in the brain results from vasodilation of the brain blood vessels and increased microvascular permeability, resulting in perivascular edema. These experimental techniques provide us with the tools to further characterize the mechanism responsible for cytokine-induced neuropsychiatric toxicity.

  17. Flow regulation in coronary vascular tree: a model study.

    Directory of Open Access Journals (Sweden)

    Xinzhou Xie

    Full Text Available Coronary blood flow can always be matched to the metabolic demand of the myocardium due to the regulation of vasoactive segments. Myocardial compressive forces play an important role in determining coronary blood flow but its impact on flow regulation is still unknown. The purpose of this study was to develop a coronary specified flow regulation model, which can integrate myocardial compressive forces and other identified regulation factors, to further investigate the coronary blood flow regulation behavior.A theoretical coronary flow regulation model including the myogenic, shear-dependent and metabolic responses was developed. Myocardial compressive forces were included in the modified wall tension model. Shear-dependent response was estimated by using the experimental data from coronary circulation. Capillary density and basal oxygen consumption were specified to corresponding to those in coronary circulation. Zero flow pressure was also modeled by using a simplified capillary model.Pressure-flow relations predicted by the proposed model are consistent with previous experimental data. The predicted diameter changes in small arteries are in good agreement with experiment observations in adenosine infusion and inhibition of NO synthesis conditions. Results demonstrate that the myocardial compressive forces acting on the vessel wall would extend the auto-regulatory range by decreasing the myogenic tone at the given perfusion pressure.Myocardial compressive forces had great impact on coronary auto-regulation effect. The proposed model was proved to be consistent with experiment observations and can be employed to investigate the coronary blood flow regulation effect in physiological and pathophysiological conditions.

  18. Effects of tempol on endothelial and vascular dysfunctions and insulin resistance induced by a high-fat high-sucrose diet in the rat.

    Science.gov (United States)

    Bourgoin, Frédéric; Bachelard, Hélène; Badeau, Mylène; Larivière, Richard; Nadeau, André; Pitre, Maryse

    2013-07-01

    We investigated the effects of treatment with tempol (an antioxidant) on vascular and metabolic dysfunction induced by a high-fat high-sucrose (HFHS) diet. Rats were randomized to receive an HFHS or chow diet with or without tempol treatment (1.5 mmol·(kg body mass)(-1)·day(-1)) for 4 weeks. Blood pressure, heart rate, and blood flow were measured in the rats by using intravascular catheters and Doppler flow probes. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic-hyperinsulinemic clamp. In-vitro studies were performed to evaluate vascular reactivity and endothelial and inducible nitric oxide synthase (eNOS; iNOS) expression in vascular and muscle tissues. Endothelin, nitrotyrosine, and NAD(P)H oxidase expressions were determined in vascular tissues, and glucose transport activity and glucose transporter 4 (GLUT4) expression were examined in muscles. Tempol treatment was found to prevent alterations in insulin sensitivity, glucose transport activity, GLUT4 expression, and vascular reactivity, and to prevent increases in plasma insulin, blood pressure, and heart rate noted in the untreated HFHS-fed rats. These were associated with increased levels of eNOS expression in vascular and muscle tissues, but reductions in nitrotyrosine, endothelin, NAD(P)H oxidase, and iNOS expressions. Therefore, oxidative stress induced by a relatively short-term HFHS diet could contribute to the early development of vascular and metabolic abnormalities in rats.

  19. Exercise Training suppresses vascular fibrosis in aging obesity induced rats

    Science.gov (United States)

    Kim, Shin Young; Lee, Jin

    2014-01-01

    [Purpose] The aim of this study was to investigate the effects of exercise training (ET) on vascular fibrosis in aging model rats with diet-induced obesity. [Methods] Twenty-four male Sprague-Dawley rats were divided into 3 groups: Aging control (A-C), A-C with high fat diet (AHF), AHF with ET (AHF + ET). Aging was induced by D-galactose (D-gal) and obesity was induced by HFD (60% fat) for 9 weeks. The experimental rats performed swimming (60 min/day, 5 days/week) for 8 weeks. All rat aorta samples were harvested for RT-PCR and morphologic analyses. [Results] The exercise training significantly decreased levels of AT-1, TGF-ß and Coll-1 gene expression compared to AHF group. The AHF + ET group showed a reduced collagen accumulation in the aorta media compared to AHF group. [Conclusion] These results suggest that ET could protect the aging obesity aorta against down-regulation of fibrotic factors (AT-1, TGF-ß and Coll-1 gene) and fibrosis by inhibition of collagen accumulation in the aorta media. PMID:25566453

  20. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

    Directory of Open Access Journals (Sweden)

    Jianhong Ye

    Full Text Available PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs, internal carotid arteries (ICAs and basal artery (BA were estimated through Transcranial Color Doppler (TCD. The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05. IMT had positive correlation with post radiation interval (p = 0.049. Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001. Plaques were more common in patients with TLN than patients without TLN (p = 0.038. In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001. Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001. CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

  1. Levamisole induced apoptosis in cultured vascular endothelial cells

    Science.gov (United States)

    Artwohl, Michaela; Hölzenbein, Thomas; Wagner, Ludwig; Freudenthaler, Angelika; Waldhäusl, Werner; Baumgartner-Parzer, Sabina M

    2000-01-01

    To better understand the anticancer activity of Levamisole (LMS), which serves as an adjuvant in colon cancer therapy in combination with 5-Fluorouracil, this study analyses LMS' ability to induce apoptosis and growth arrest in cultured human micro- and macrovascular endothelial cells (ECs) and fibroblasts. Cells exposed (24 h) to Levamisole (range: 0.5–2 mmol l−1) alone or in combination with antioxidants (10 mmol l−1 glutathione or 5 mmol l−1 N-Acetylcysteine or 0.1 mmol l−1 Tocopherol) were evaluated for apoptosis (3H-thymidine assays, in situ staining), mRNA/protein expression (Northern/Western blot), and proliferation (3H-thymidine incorporation). Levamisole dose-dependently increased apoptosis in ECs to 230% (HUVECs-human umbilical vein ECs), 525% (adult human venous ECs) and 600% (human uterine microvascular ECs) but not in fibroblasts compared to control cells (set as 100%). Levamisole increased in ECs integrin-dependent matrix adhesion, inhibited proliferation (−70%), reduced expression of survival factors such as clusterin (−30%), endothelin-1 (−43%), bcl-2 (−34%), endothelial NO-synthase (−32%) and pRb (Retinoblastoma protein: −89%), and increased that of growth arrest/death signals such as p21 (+73%) and bak (+50%). LMS (2 mmol l−1)-induced apoptosis was inhibited by glutathione (−50%) and N-Acetylcysteine (−36%), which also counteracted reduction by Levamisole of pRb expression, suggesting reactive oxygen species and pRb play a role in these processes. The ability of LMS to selectively induce apoptosis and growth arrest in endothelial cells potentially hints at vascular targeting to contribute to Levamisole's anticancer activity. PMID:11139434

  2. Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

    Science.gov (United States)

    Pleiner, Johannes; Heere-Ress, Elisabeth; Langenberger, Herbert; Sieder, Anna E; Bayerle-Eder, Michaela; Mittermayer, Fritz; Fuchsjäger-Mayrl, Gabriele; Böhm, Johannes; Jansen, Burkhard; Wolzt, Michael

    2002-01-01

    Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

  3. Effect of crocetin on vascular smooth muscle cells migration induced by advanced glycosylation end products.

    Science.gov (United States)

    Xiang, Min; Yang, Runlin; Zhang, Yaqin; Wu, Pingping; Wang, Lizhen; Gao, Zhenyu; Wang, Jianmei

    2017-02-13

    Crocetin is a major active constituent of Gardenia jasminoides J. Ellis, and can aid in the prevention of cardiovascular disease. The effect and possible mechanism of crocetin on the migration of vascular smooth muscle cells (VSMCs) induced by advanced glycosylation end products (AGEs) were investigated. VSMCs were pre-incubated with or without crocetin and exposed to AGEs subsequently. The invasion of the cells was investigated using a 24-well Cell Invasion Chamber. The anti-proliferative activity of crocetin was evaluated by MTT assay and VSMCs cell-cycle distribution was examined by flow cytometry. Cytokine TNF-α and IL-6 secreted by VSMCs and the amount of matrix metalloproteinase MMP-2 and MMP-9 in the culture supernatant were detected by ELISA. The expression level of RAGE (AGEs receptor), in cells was analyzed by western blot. The results demonstrated that AGEs increased about two-fold migration of VSMCs compared with control (OD=0.778±0.191 vs OD=0.413±0.214, Pvalue of MMP-2 and MMP-9 compared with the AGEs group (2.81±0.35ng/ml vs 6.40±0.85ng/ml, 2.69±0.25ng/ml vs 4.32±0.57ng/ml, respectively). In summary, crocetin inhibits the migration of VSMCs induced by AGEs through RAGE-dependent signaling pathway. And it is meaningful to diabetic vascular complications.

  4. Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation

    Directory of Open Access Journals (Sweden)

    Nemmar A

    2014-06-01

    Full Text Available Abderrahim Nemmar,1 Sulayma Albarwani,2 Sumaya Beegam,1 Priya Yuvaraju,1 Javed Yasin,3 Samir Attoub,4 Badreldin H Ali5 1Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Sultanate of Oman; 3Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 4Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 5Department of Pharmacology, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Sultanate of Oman Abstract: Amorphous silica nanoparticles (SiNPs are being used in biomedical, pharmaceutical, and many other industrial applications entailing human exposure. However, their potential vascular and systemic pathophysiologic effects are not fully understood. Here, we investigated the acute (24 hours systemic toxicity of intraperitoneally administered 50 nm and 500 nm SiNPs in mice (0.5 mg/kg. Both sizes of SiNPs induced a platelet proaggregatory effect in pial venules and increased plasma concentration of plasminogen activator inhibitor-1. Elevated plasma levels of von Willebrand factor and fibrinogen and a decrease in the number of circulating platelets were only seen following the administration of 50 nm SiNPs. The direct addition of SiNPs to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced with 50 nm SiNPs. Both sizes of SiNPs increased lactate dehydrogenase activity and interleukin 1β concentration. However, tumor necrosis factor α concentration was only increased after the administration of 50 nm SiNPs. Nevertheless, plasma markers of oxidative stress, including 8-isoprostane

  5. Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Kelly; Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Schnell, Susanne; Barker, Alex J.; Garcia, Julio; Chowdhary, Varun; Carr, James [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Lorenz, Ramona [University Medical Center Freiburg, Department of Radiology, Freiburg (Germany); Rose, Michael [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Robinson, Joshua D. [Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Cardiology, Chicago, IL (United States); Rigsby, Cynthia K. [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-10-15

    Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R{sup 2}=0.50, P=0.02; SVC to LPA: R{sup 2}=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability. (orig.)

  6. Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI.

    Science.gov (United States)

    Jarvis, Kelly; Schnell, Susanne; Barker, Alex J; Garcia, Julio; Lorenz, Ramona; Rose, Michael; Chowdhary, Varun; Carr, James; Robinson, Joshua D; Rigsby, Cynthia K; Markl, Michael

    2016-10-01

    Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R(2)=0.50, P=0.02; SVC to LPA: R(2)=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability.

  7. Vascular Function and Regulation of Blood Flow in Resting and Contracting Skeletal Muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin

    importance. The present work provides new insight in to vasodilator interactions important for exercise hyperemia and sheds light on mechanisms important for vascular function and regulation of skeletal muscle blood flow in essential hypertension (high blood pressure) and aging and identifies mechanisms...... by which physical activity affects the function of the vascular network. Conclusion The vasodilators ATP and adenosine stimulate the nitric oxide and prostanoid systems in skeletal muscle. These vasodilator interactions may, at least in part, explain the central role of nitric oxide and prostanoids...... that no single compound can explain exercise hyperemia and indicates that any condition associated with reduced oxygen delivery needs to be investigated independently. Physical activity can attenuate or even counteract the effects of essential hypertension and aging on vascular function and exercise hyperemia....

  8. Efficient blood flow visualization using flowline extraction and opacity modulation based on vascular structure analysis.

    Science.gov (United States)

    Kwon, Ohjae; Lee, Jeongjin; Kim, Bohyoung; Shin, Juneseuk; Shin, Yeong-Gil

    2017-03-01

    With the recent advances regarding the acquisition and simulation of blood flow data, blood flow visualization has been widely used in medical imaging for the diagnosis and treatment of pathological vessels. In this paper, we present a novel method for the visualization of the blood flow in vascular structures. The vessel inlet or outlet is first identified using the orthogonality metric between the normal vectors of the flow velocity and vessel surface. Then, seed points are generated on the identified inlet or outlet by Poisson disk sampling. Therefore, it is possible to achieve the automatic seeding that leads to a consistent and faster flow depiction by skipping the manual location of a seeding plane for the initiation of the line integration. In addition, the early terminated line integration in the thin curved vessels is resolved through the adaptive application of the tracing direction that is based on the flow direction at each seed point. Based on the observation that blood flow usually follows the vessel track, the representative flowline for each branch is defined by the vessel centerline. Then, the flowlines are rendered through an opacity assignment according to the similarity between their shape and the vessel centerline. Therefore, the flowlines that are similar to the vessel centerline are shown transparently, while the different ones are shown opaquely. Accordingly, the opacity modulation method enables the flowlines with an unusual flow pattern to appear more noticeable, while the visual clutter and line occlusion are minimized. Finally, Hue-Saturation-Value color coding is employed for the simultaneous exhibition of flow attributes such as local speed and residence time. The experiment results show that the proposed technique is suitable for the depiction of the blood flow in vascular structures. The proposed approach is applicable to many kinds of tubular structures with embedded flow information.

  9. Hyperoside inhibits high-glucose-induced vascular inflammation in vitro and in vivo.

    Science.gov (United States)

    Ku, Sae-Kwang; Kwak, Soyoung; Kwon, O-Jun; Bae, Jong-Sup

    2014-10-01

    Hyperoside, an active compound from the genera of Hypericum and Crataegus, was reported to have antioxidant, antihyperglycemic, anticancer, anti-inflammatory, and anticoagulant activities. Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether hyperoside can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB. Remarkably, all of the above-mentioned vascular inflammatory effects of HG were attenuated by pretreatment with hyperoside. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications; therefore, our results suggest that hyperoside may have significant therapeutic benefits against diabetic complications and atherosclerosis.

  10. The role of vascular peroxidase 1 in ox-LDL-induced vascular smooth muscle cell calcification.

    Science.gov (United States)

    Tang, Yixin; Xu, Qian; Peng, Haiyang; Liu, Zhaoya; Yang, Tianlun; Yu, Zaixin; Cheng, Guangjie; Li, Xiaohui; Zhang, Guogang; Shi, Ruizheng

    2015-12-01

    Reactive oxygen species (ROS)-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) is associated with the pathogenesis of vascular calcification. Vascular peroxidase 1 (VPO1), a peroxidase in the cardiovascular system, utilizes the hydrogen peroxide (H2O2) produced by co-expressed NADPH oxidases to produce hypochlorous acid (HOCl) and catalyze peroxidative reactions. The aim of this study was to determine whether VPO1 plays a role in the osteogenic differentiation of VSMCs in the setting of the vascular calcification induced by oxidized low-density lipoprotein (ox-LDL). In cultured primary rat VSMCs, we observed that the expression of VPO1 was significantly increased in combination with increases in calcification, as demonstrated via increased mineralization, as well as increased alkaline phosphatase (ALP) activity and up-regulated runt-related transcription factor 2 (Runx2) expression in ox-LDL-treated cells. Ox-LDL-induced VSMC calcification and Runx2 expression were both inhibited by knockdown of VPO1 using a small interfering RNA or by an NADPH oxidase inhibitor. Moreover, the knockdown of VPO1 in VSMCs suppressed the production of HOCl and the phosphorylation of AKT, ERK and P38 MAPK. Furthermore, HOCl treatment facilitated the phosphorylation of AKT, ERK1/2 and P38 MAPK and the expression of Runx2, whereas LY294002 (a specific inhibitor of PI3K), U0126 (a specific inhibitor of ERK1/2) and SB203580 (a specific inhibitor of P38 MAPK) significantly attenuated the HOCl-induced up-regulation of Runx2. Collectively, these results demonstrated that VPO1 promotes ox-LDL-induced VSMC calcification via the VPO1/HOCl/PI3K/AKT, ERK1/2, and P38 MAPK/Runx2 signaling pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Development of an Open Source Image-Based Flow Modeling Software - SimVascular

    Science.gov (United States)

    Updegrove, Adam; Merkow, Jameson; Schiavazzi, Daniele; Wilson, Nathan; Marsden, Alison; Shadden, Shawn

    2014-11-01

    SimVascular (www.simvascular.org) is currently the only comprehensive software package that provides a complete pipeline from medical image data segmentation to patient specific blood flow simulation. This software and its derivatives have been used in hundreds of conference abstracts and peer-reviewed journal articles, as well as the foundation of medical startups. SimVascular was initially released in August 2007, yet major challenges and deterrents for new adopters were the requirement of licensing three expensive commercial libraries utilized by the software, a complicated build process, and a lack of documentation, support and organized maintenance. In the past year, the SimVascular team has made significant progress to integrate open source alternatives for the linear solver, solid modeling, and mesh generation commercial libraries required by the original public release. In addition, the build system, available distributions, and graphical user interface have been significantly enhanced. Finally, the software has been updated to enable users to directly run simulations using models and boundary condition values, included in the Vascular Model Repository (vascularmodel.org). In this presentation we will briefly overview the capabilities of the new SimVascular 2.0 release. National Science Foundation.

  12. Micro-PIV quantification of capillary blood flow redistribution caused by laser-assisted vascular occlusion

    Science.gov (United States)

    Kurochkin, Maxim A.; Stiukhina, Elena S.; Fedosov, Ivan V.; Postnov, Dmitry E.; Tuchin, Valery V.

    2016-04-01

    We propose μPIV-based technique for quantitative assessment of blood flow redistribution in microcirculatory networks. Our approach is based on per-segment averaging of measured quantities so we can avoid most of problems that are typical for point-wise measurements. The key point of our technique is the digital processing algorithms of recorded data that include: capillary network axial line construction; interrogation regions centering; blood flow velocity local estimate using PIV approach; blood flow velocity calculation by means of averaging over entire vessel segment; the calculation of blood volume flow rate map. We illustrate the application of developed technique with in vivo measurements and blood flow velocity map reconstruction for chorioallantoic membrane (CAM) of chicken embryo, in which the local vascular occlusion was produced using continuous wave laser light irradiation..

  13. Vascular Function and Regulation of Blood Flow in Resting and Contracting Skeletal Muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin

    in the regulation of exercise hyperemia. Furthermore, blood flow to contracting leg skeletal muscles is reduced both in essential hypertension and with aging. The potential difference in vasoactive system(s) responsible for the reduction in blood flow in the two conditions is in agreement with the suggestion......The precise matching of blood flow, oxygen delivery and metabolism is essential as it ensures that any increase in muscle work is precisely matched by increases in oxygen delivery. Therefore, understanding the control mechanisms of skeletal muscle blood flow regulation is of great biological...... importance. The present work provides new insight in to vasodilator interactions important for exercise hyperemia and sheds light on mechanisms important for vascular function and regulation of skeletal muscle blood flow in essential hypertension (high blood pressure) and aging and identifies mechanisms...

  14. Doxorubicin-induced vascular toxicity--targeting potential pathways may reduce procoagulant activity.

    Directory of Open Access Journals (Sweden)

    Irit Ben Aharon

    Full Text Available INTRODUCTION: Previous study in mice using real-time intravital imaging revealed an acute deleterious effect of doxorubicin (DXR on the gonadal vasculature, as a prototype of an end-organ, manifested by a reduction in blood flow and disintegration of the vessel wall. We hypothesized that this pattern may represent the formation of microthrombi. We aimed to further characterize the effect of DXR on platelets' activity and interaction with endothelial cells (EC and to examine potential protectants to reduce DXR acute effect on the blood flow. METHODS: The effect of DXR on platelet adhesion and aggregation were studied in vitro. For in vivo studies, mice were injected with either low molecular weight heparin (LMWH; Enoxaparin or with eptifibatide (Integrilin(© prior to DXR treatment. Testicular arterial blood flow was examined in real-time by pulse wave Doppler ultrasound. RESULTS: Platelet treatment with DXR did not affect platelet adhesion to a thrombogenic surface but significantly decreased ADP-induced platelet aggregation by up to 40% (p<0.001. However, there was a significant increase in GPIIbIIIa-mediated platelet adhesion to DXR-exposed endothelial cells (EC; 5.7-fold; p<0.001 reflecting the toxic effect of DXR on EC. The testicular arterial blood flow was preserved in mice pre-treated with LMWH or eptifibatide prior to DXR (P<0.01. CONCLUSIONS: DXR-induced acute vascular toxicity may involve increased platelet-EC adhesion leading to EC-bound microthrombi formation resulting in compromised blood flow. Anti-platelet/anti-coagulant agents are effective in reducing the detrimental effect of DXR on the vasculature and thus may serve as potential protectants to lessen this critical toxicity.

  15. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Schreuder, T.H.A.; Lotringen, J.H. van; Hopman, M.T.E.; Thijssen, D.H.J.

    2014-01-01

    Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact

  16. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Schreuder, T.H.A.; Lotringen, J.H. van; Hopman, M.T.E.; Thijssen, D.H.J.

    2014-01-01

    Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact

  17. Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation

    Science.gov (United States)

    Bonacina, F.; Barbieri, S.S.; Cutuli, L.; Amadio, P.; Doni, A.; Sironi, M.; Tartari, S.; Mantovani, A.; Bottazzi, B.; Garlanda, C.; Tremoli, E.; Catapano, A.L.; Norata, G.D.

    2016-01-01

    Aim The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis. Methods and results PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (− 80.36 ± 11.5% and − 95.53 ± 4.46%), while in WT mice transplanted with bone marrow from either WT or PTX3 KO mice, the reduction was less dramatic (− 45.55 ± 1.37% and − 53.39 ± 9.8%), thus pointing to a protective effect independent of a hematopoietic cell's derived PTX3. By using P-selectin/PTX3 double KO mice, we further excluded a role for P-selectin, a target of PTX3 released by neutrophils, in vascular protection played by PTX3. In agreement with a minor role for hematopoietic cell-derived PTX3, platelet activation (assessed by flow cytometric expression of markers of platelet activation) was similar in PTX3 KO and WT mice as were haemostatic properties. Histological analysis indicated that PTX3 localizes within the thrombus and the vessel wall, and specific experiments with the N-terminal and the C-terminal PTX3 domain showed the ability of PTX3 to selectively dampen either fibrinogen or collagen induced platelet adhesion and aggregation. Conclusion PTX3 interacts with fibrinogen and collagen and, by dampening their pro-thrombotic effects, plays a protective role during arterial thrombosis. PMID:26976330

  18. Phoretic flow induced by asymmetric confinement

    CERN Document Server

    Lisicki, Maciej; Lauga, Eric

    2016-01-01

    Internal phoretic flows due to the interactions of solid boundaries with local chemical gradients may be created using chemical patterning. Alternatively, we demonstrate here that internal flows might also be induced by geometric asymmetries of chemically-homogeneous surfaces. We characterise the circulatory flow created in a cavity enclosed between two eccentric cylindrical walls of uniform chemical activity. Local gradients of the diffusing solute induce a slip flow along the surface of the cylinders, leading to a circulatory bulk flow pattern which can be solved analytically in the diffusive limit. The flow strength can be controlled by adjusting the relative positions of the cylinders and an optimal configuration is identified. These results provide a model system for tunable phoretic pumps.

  19. Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization.

    Science.gov (United States)

    da Palma, Renata K; Campillo, Noelia; Uriarte, Juan J; Oliveira, Luis V F; Navajas, Daniel; Farré, Ramon

    2015-09-01

    Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (pperfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (pperfusion mechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity.

  20. Simulation of blood flow in a small-diameter vascular graft model with a swirl (spiral) flow guider

    Institute of Scientific and Technical Information of China (English)

    Robert; GUIDOIN

    2008-01-01

    Small-diameter vascular grafts are in large demand for coronary and peripheral bypass procedures, but present products still fail in long-term clinical application. In the present communication, a new type of small-diameter graft with a swirl flow guider was proposed to improve graft patency rate. Flow pattern in the graft was simulated numerically and compared with that in a conventional graft. The numerical results revealed that the swirl flow guider could indeed make the blood flow rotate in the new graft. The swirling flow distal to the flow guider significantly altered the flow pattern in the new graft and the ve- locity profiles were re-distributed. Due to the swirling flow, the blood velocity near the vessel wall and wall shear rate were greatly enhanced. We believe that the increased blood velocity near the wall and the wall shear rate can impede the occurrence of acute thrombus formation and intimal hyperplasia, hence can improve the graft patency rate for long-term clinical use.

  1. Simulation of blood flow in a small-diameter vascular raft model with a swirl (spiral) flow guider

    Institute of Scientific and Technical Information of China (English)

    ZHANG ZhiGuo; FAN YuBo; DENG XiaoYan; WANG GuiXue; ZHANG He; Robert GUIDOIN

    2008-01-01

    Small-dlameter vascular grafts are in large demand for coronary and peripheral bypass procedures, but present products still fail in long-term clinical application. In the present communication, a new type of small-diameter graft with a swirl flow guider was proposed to improve graft patency rate. Flow pattern in the graft was simulated numerically and compared with that in a conventional graft. The numerical results revealed that the swirl flow guider couldindeed make the blood flow rotate in the new graft. The swirling flow distal to the flow guider significantly altered the flow pattern in the new graft and the ve-locity profiles were re-distributed. Due to the swirling flow, the blood velocity near the vessel wall and wall shear rate were greatly enhanced. We believe that the increased blood velocity near the wall and the wall shear rate can impede the occurrence of acute thrombus formation and intimal hyperplasia, hence can improve the graft patency rate for long-term clinical use.

  2. Uncooled infrared camera for the noninvasive visualization of the vascular flow in an anastomotic vessel during neurological surgery: technical note.

    Science.gov (United States)

    Otani, Naoki; Ishihara, Miya; Nakai, Kanji; Fujita, Masanori; Wada, Kojiro; Mori, Kentaro

    2014-06-17

    We herein present our experience to assess intraoperative confirmation of vascular patency with an uncooled infrared camera in extracranial-intracranial (EC-IC) bypass surgery. This camera had distinguishing characteristics, including its small size, light weight, and adequate temperature resolution (camera to assess the vascular flow of the end-to-side anastomosis model in rats. In addition, we evaluated the vascular flow in continuous clinical series using this infrared camera during EC-IC bypass in 14 patients (17 sides). This infrared camera offers real-time information on the vascular patency of end-to-side anastomosis vessels of all relevant diameters. The spatial resolution and image quality are satisfactory, and the procedure can be safely repeatable. We have shown that the infrared camera could be a new and feasible technology for intraoperative imaging of the vascular flow and is considered to be clinically useful during cerebrovascular surgery.

  3. Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability

    Institute of Scientific and Technical Information of China (English)

    Yun-Liang Cui; Sheng Zhang; Zhao-Tao Tian; Zhao-Fen Lin; De-Chang Chen

    2016-01-01

    Background:Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis.Dysfunction of the latter is an underlying cause of various organ pathologies.In a previous study,we showed that rhubarb,a traditional Chinese medicine,protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia.In this study,we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability.Methods:Rhubarb monomers were extracted and purified by a series of chromatography approaches.The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR),carbon-13 NMR,and distortionless enhancement by polarization transfer magnetic resonance spectroscopy.We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert.We measured the HUVEC permeability,proliferation,and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay,3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay,and enzyme-linked immunosorbent assay,respectively,in response to treatment with MMP9 and/or rhubarb monomers.Results:A total of 21 rhubarb monomers were extracted and identified.MMP9 significantly increased the permeability of the HUVEC monolayer,which was significantly reduced by five individual rhubarb monomer (emodin,3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid,1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose,daucosterol linoleate,and rhein) or a combination of all five monomers (1 μmol/L for each monomer).Mechanistically,the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation.In addition,MMP9 stimulated the secretion of VE-cadherin into the culture medium,which was significantly inhibited by the five-monomer mixture.Conclusions:The rhubarb mixture of emodin,3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid,1-O-caffeoyl-2-(4-hydroxyl

  4. Orientin inhibits high glucose-induced vascular inflammation in vitro and in vivo.

    Science.gov (United States)

    Ku, Sae-Kwang; Kwak, Soyoung; Bae, Jong-Sup

    2014-12-01

    Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Orientin, a C-glycosyl flavonoid, is known to have anxiolytic and antioxidative activity. In this study, we assessed whether orientin can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, the expression of cell adhesion molecules (CAMs), the formation of reactive oxygen species (ROS), and the activation of nuclear factor kappa B (NF-κB). Remarkably, the vascular inflammatory effects of HG were attenuated by pretreatment with orientin. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that orientin may have significant benefits in the treatment of diabetic complications and atherosclerosis.

  5. Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Vascular Changes Induced by Sunitinib in Papillary Renal Cell Carcinoma Xenograft Tumors

    Directory of Open Access Journals (Sweden)

    Gilda G. Hillman

    2009-09-01

    Full Text Available To investigate further the antiangiogenic potential of sunitinib for renal cell carcinoma (RCC treatment, its effects on tumor vasculature were monitored by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI using an orthotopic KCI-18 model of human RCC xenografts in nude mice. Tumor-bearing mice were treated with various doses of sunitinib, and vascular changes were assessed by DCE-MRI and histologic studies. Sunitinib induced dose-dependent vascular changes, which were observed both in kidney tumors and in normal kidneys by DCE-MRI. A dosage of 10 mg/kg per day caused mild changes in Gd uptake and clearance kinetics in kidney tumors. A dosage of 40 mg/kg per day induced increased vascular tumor permeability with Gd retention, probably resulting from the destruction of tumor vasculature, and also caused vascular alterations of normal vessels. However, sunitinib at 20 mg/kg per day caused increased tumor perfusion and decreased vascular permeability associated with thinning and regularization of tumor vessels while mildly affecting normal vessels as confirmed by histologic diagnosis. Alterations in tumor vasculature resulted in a significant inhibition of KCI-18 RCC tumor growth at sunitinib dosages of 20 and 40 mg/kg per day. Sunitinib also exerted a direct cytotoxic effect in KCI-18 cells in vitro. KCI-18 cells and tumors expressed vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β molecular targets of sunitinib that were modulated by the drug treatment. These data suggest that a sunitinib dosage of 20 mg/kg per day, which inhibits RCC tumor growth and regularizes tumor vessels with milder effects on normal vessels, could be used to improve blood flow for combination with chemotherapy. These studies emphasize the clinical potential of DCE-MRI in selecting the dose and schedule of antiangiogenic compounds.

  6. Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification

    Directory of Open Access Journals (Sweden)

    Sayo Koike

    2016-09-01

    Full Text Available Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD. To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs stimulated calcium deposition in vascular smooth muscle cells (VSMCs through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5 was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA. Apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD(PH oxidase components including Nox4 and p22phox, and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22phox. Double knockdown of Nox4 and p22phox showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD(PH oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD.

  7. Effects of vascular elastosis on uterine blood flow and perfusion in anesthetized mares.

    Science.gov (United States)

    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J

    2015-04-01

    In the uterus of the mare, data obtained using transrectal Doppler ultrasonography indicate that uterine blood flow (UBF) is dynamic and changes throughout the estrous cycle. Degenerative lesions in the uterus are associated with subfertility and infertility. Among these lesions, vascular elastosis has been reported in aged, multiparous, and infertile mares. Angiosis of the uterine vasculature could potentially compromise UBF. The objectives of this experiment are to determine levels of UBF and perfusion of reproductively healthy mares and compare them to levels of subfertile/infertile mares affected by uterine vascular elastosis. Twenty mares were classified on the basis of degree of vascular degeneration and stage of cycle. A fluorescent microsphere technique was used to measure reproductive organ perfusion, where microspheres were injected into the left ventricle of the heart and became trapped in capillary beds in proportion to blood flow and tissue perfusion. The reproductive tract was removed, sectioned, and the fluorescent intensity evaluated to measure blood flow and perfusion. Additionally, full-thickness samples of the uterine wall were examined postmortem to further assess the degree of vascular degeneration in all layers of uterine wall. The mean value of uterine perfusion for the control mares during estrus (n = 5) was higher (P perfusion was not different (P > 0.05) during estrus (n = 5) and diestrus (n = 5); 5.9 and 7.2 mL/min/100g, respectively. Uterine perfusion in subfertile/infertile mares affected by elastosis was lower than that of control mares during both estrus (P perfusion between the control and elastosis groups indicate that elastosis of the uterine vasculature is associated with decreased uterine perfusion during both phases of the estrous cycle. In the uterus, a compromise in UBF could have implications in endometrial glandular development, postbreeding endometritis, uterine clearance, development of the conceptus, and

  8. Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Xuemin; Hu, Wenyu; Wu, Fang; Yuan, Xue; Hu, Jian

    2015-08-01

    Shikonin is a naphthoquinone compound extracted from the Chinese herb purple gromwell. Shikonin has broad antibacterial, anti-inflammatory, and antitumor activities. The tumor necrosis factor-α (TNF-α)-induced proliferation and invasion of vascular smooth muscle cells (VSMCs) is an important factor that contributes to atherosclerosis. The effects of shikonin on the proliferation and apoptosis of VSMCs have been reported; however, the function of shikonin on TNF-α-mediated growth and invasion of VSMCs during atherosclerosis remains unclear. In this study, we used Western blot, flow cytometry, real-time quantitative PCR, and enzyme-linked immunosorbent assay to investigate the effect of shikonin on the TNF-α-induced growth and invasion of VSMCs and to determine the underlying mechanism. Our results showed that shikonin inhibits the TNF-α-mediated growth and invasion. Further study revealed that shikonin regulates the activation of nuclear factor kappa B and phosphatidyl inositol 3-kinase signaling pathways; modulates the expression of cyclin D1, cyclin E, B-cell lymphoma 2, and Bax; activates caspase-3 and caspase-9; induces cell cycle arrest; and promotes the apoptosis of VSMCs. Together, our results indicate that shikonin may become a promising agent for the treatment of atherosclerosis and they also establish foundation for the development of anti-atherosclerosis drugs.

  9. Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion.

    Science.gov (United States)

    Li, Ting-Ting; Zhang, Yi-Shuai; He, Lan; Liu, Bin; Shi, Rui-Zheng; Zhang, Guo-Gang; Peng, Jun

    2012-07-01

    Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.

  10. Protective Effect of Salicornia europaea Extracts on High Salt Intake-Induced Vascular Dysfunction and Hypertension

    Science.gov (United States)

    Panth, Nisha; Park, Sin-Hee; Kim, Hyun Jung; Kim, Deuk-Hoi; Oak, Min-Ho

    2016-01-01

    High salt intake causes and aggravates arterial hypertension and vascular dysfunction. We investigated the effect of Salicornia europaea extracts (SE) on vascular function and blood pressure. SE constituents were analyzed using high performance liquid chromatography, and SE’s effect on vascular function was evaluated in isolated porcine coronary arteries. SE’s vascular protective effect was also evaluated in vivo using normotensive and spontaneous hypertensive rats (SHRs). SE mainly contained sodium chloride (55.6%), 5-(hydroxymethyl)furfural, p-coumaric acid, and trans-ferulic acid. High sodium (160 mmol/L) induced vascular dysfunction; however, SE containing the same quantity of sodium did not cause vascular dysfunction. Among the compounds in SE, trans-ferulic acid accounts for the vascular protective effect. Normotensive rats fed a high-salt diet showed significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), which decreased significantly in the SE-treated groups. In SHRs, high edible salt intake significantly increased SBP, DBP, and MAP, but SE intake was associated with a significantly lower MAP. Thus, SE did not induce vascular dysfunction, and trans-ferulic acid might be at least partly responsible for the vasoprotective effect of SE. Taken together, SE could be used as an alternative to purified salt to prevent and ameliorate hypertension. PMID:27455235

  11. Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2013-01-01

    Full Text Available Pyruvate is an endogenous antioxidant substance. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP on retinal vascular injury in diabetic retinopathy. To investigate the protective effect of EP on vascular cell apoptosis and blood-retinal barrier (BRB breakage, we have used intravitreally methylglyoxal-(MGO- injected rat eyes. Apoptosis of the retinal vascular cell that was stimulated by the intravitreal injection of MGO was evidently attenuated by the EP treatment. EP exerts inhibitory effect on MGO-induced vascular cell apoptosis by blocking oxidative injury. In addition, EP treatment prevented MGO-induced BRB breakage and the degradation of occludin, an important tight junction protein. These observations suggest that EP acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal vessels.

  12. Juxta-vascular nodule segmentation based on flow entropy and geodesic distance.

    Science.gov (United States)

    Sun, Shenshen; Guo, Yang; Guan, Yubao; Ren, Huizhi; Fan, Linan; Kang, Yan

    2014-07-01

    Computed aided diagnosis of lung CT data is a new quantitative analysis technique to distinguish malignant nodules from benign ones. Nodule growth rate is a key indicator to discriminate between benign and malignant nodules. Accurate nodule segmentation is the essential for calculating the nodule growth rate. However, it is difficult to segment juxta-vascular nodules, due to the similar gray levels in nodule and attached blood vessels. To distinguish the nodule region from the adjacent vessel region, a flowing direction feature, referred to as the direction of the normal vector for a pixel, is introduced. Since blood is flowing in one single direction through a vessel, the normal vectors of pixels in the vessel region typically point in similar orientations while the directions of those in the nodule region can be viewed as disorganized. The entropy value of the flowing direction features in a neighboring region for a vessel pixel is smaller than that for a nodule pixel. Moreover, vessel pixels typically have a larger geodesic distance to the nodule center than nodule pixels. Based on k -means clustering method, the flow entropy, combined with the geodesic distance, is used to segment vessel attached nodules. The validation of the proposed segmentation algorithm was carried out on juxta-vascular nodules, identified in the Chinalung-CT screening trial and on Lung Image Database Consortium (LIDC) dataset. In fully automated mode, accuracies of 92.9% (26/28), 87.5%(7/8), and 94.9% (149/157) are reached for the outlining of juxta-vascular nodules in the Chinalung-CT, and the first and second datasets of LIDC, respectively. Furthermore, it is demonstrated that the proposed method has low time complexity and high accuracies.

  13. Bellows flow-induced vibrations

    Science.gov (United States)

    Johnson, J. E.; Deffenbaugh, D. M.; Astleford, W. J.; Gerlach, C. R.

    1979-01-01

    Results of theoretical and experimental investigations of bellows typical of those found in space shuttle external tanks are presented. Correlation parameters are identified which generalize the alternating stress calculations cited in an earlier study. Alternating stress amplitudes and mean stress levels form the basis of a fatigue analysis incorporating seven ordinate charts for 347 stainless steel, alloy 21 6-9, and Inco 718. A crack propagation model is included with a program for computing bellows fatigue life. Two phase flow and material hardness properties are discussed.

  14. p66Shc regulates renal vascular tone in hypertension-induced nephropathy.

    Science.gov (United States)

    Miller, Bradley; Palygin, Oleg; Rufanova, Victoriya A; Chong, Andrew; Lazar, Jozef; Jacob, Howard J; Mattson, David; Roman, Richard J; Williams, Jan M; Cowley, Allen W; Geurts, Aron M; Staruschenko, Alexander; Imig, John D; Sorokin, Andrey

    2016-07-01

    Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy.

  15. Induced airflow in flying insects II. Measurement of induced flow.

    Science.gov (United States)

    Sane, Sanjay P; Jacobson, Nathaniel P

    2006-01-01

    The flapping wings of insects and birds induce a strong flow over their body during flight. Although this flow influences the sensory biology and physiology of a flying animal, there are very little data on the characteristics of this self-generated flow field or its biological consequences. A model proposed in the companion paper estimated the induced flow over flying insects. In this study, we used a pair of hot wire anemometers to measure this flow at two locations near the body of a tethered flapping hawk moth, Manduca sexta. The axial inflow anemometer measured the airflow prior to its entry into the stroke plane, whereas the radial outflow anemometer measured the airflow after it crossed the stroke plane. The high temporal resolution of the hot wire anemometers allowed us to measure not only the mean induced flow but also subtle higher frequency disturbances occurring at 1-4 times the wing beat frequency. These data provide evidence for the predictions of a mathematical model proposed in the companion paper. Specifically, the absolute value of the measured induced flow matches the estimate of the model. Also, as predicted by the model, the induced flow varies linearly with wing beat frequency. Our experiments also show that wing flexion contributes significantly to the observed higher frequency disturbances. Thus, the hot wire anemometry technique provides a useful means to quantify the aerodynamic signature of wing flexion. The phasic and tonic components of induced flow influence several physiological processes such as convective heat loss and gas exchange in endothermic insects, as well as alter the nature of mechanosensory and olfactory stimuli to the sensory organs of a flying insect.

  16. Twenty-four hour blood flow in the forefoot after reconstructive vascular surgery

    DEFF Research Database (Denmark)

    Jelnes, R

    1986-01-01

    Local blood flow in the forefoot (SBF) was measured continuously during 24 hours by 133xenon clearance technique in 10 patients prior to and at least 1 year after successful reconstructive vascular surgery for severe arterial insufficiency (mean: 18 months, range: 12-36). A group of 10 patients...... with normal peripheral circulation served as a control group. In spite of a considerable increase of the ankle/arm systolic blood pressure index--preoperative: 0.30 +/- 0.12, postoperative: 0.78 +/- 0.28 (mean +/- 1 SD)--the SBF decreased by 50% (p less than 0.001) following reconstructive vascular surgery...... are explained by the reappearance of peripheral vasoregulatory mechanisms. Postreconstructive hyperemia was evaluated by the same technique. The changes in SBF following surgery in the positions supine, awake and supine, asleep were found to be insignificant (0.80 less than p less than 0.90). It is concluded...

  17. Shear wave dispersion behaviors of soft, vascularized tissues from the microchannel flow model.

    Science.gov (United States)

    Parker, K J; Ormachea, J; McAleavey, S A; Wood, R W; Carroll-Nellenback, J J; Miller, R K

    2016-07-07

    The frequency dependent behavior of tissue stiffness and the dispersion of shear waves in tissue can be measured in a number of ways, using integrated imaging systems. The microchannel flow model, which considers the effects of fluid flow in the branching vasculature and microchannels of soft tissues, makes specific predictions about the nature of dispersion. In this paper we introduce a more general form of the 4 parameter equation for stress relaxation based on the microchannel flow model, and then derive the general frequency domain equation for the complex modulus. Dispersion measurements in liver (ex vivo) and whole perfused placenta (post-delivery) correspond to the predictions from theory, guided by independent stress relaxation measurements and consideration of the vascular tree structure.

  18. Wall shear stress measurement method based on parallel flow model near vascular wall in echography

    Science.gov (United States)

    Shimizu, Motochika; Tanaka, Tomohiko; Okada, Takashi; Seki, Yoshinori; Nishiyama, Tomohide

    2017-07-01

    A high-risk vessel of arteriosclerosis is detected by assessing wall shear stress (WSS), which is calculated from the distribution of velocity in a blood flow. A novel echographic method for measuring WSS, which aims to distinguish a normal vessel from a high-risk vessel, is proposed. To achieve this aim, the measurement error should be less than 28.8%. The proposed method is based on a flow model for the area near a vascular wall under a parallel-flow assumption to avoid the influences of error factors. This was verified by an in vitro experiment in which the WSS of a carotid artery phantom was measured. According to the experimental results, the WSS measured by the proposed method correlated with the ground truth measured by particle image velocimetry; in particular, the correlation coefficient and measurement error between them were respectively 0.70 and 27.4%. The proposed method achieved the target measurement performance.

  19. Twenty-four hour blood flow in the forefoot after reconstructive vascular surgery

    Energy Technology Data Exchange (ETDEWEB)

    Jelnes, R.

    1986-08-01

    Local blood flow in the forefoot (SBF) was measured continuously during 24 hours by 133xenon clearance technique in 10 patients prior to and at least 1 year after successful reconstructive vascular surgery for severe arterial insufficiency (mean: 18 months, range: 12-36). A group of 10 patients with normal peripheral circulation served as a control group. In spite of a considerable increase of the ankle/arm systolic blood pressure index--preoperative: 0.30 +/- 0.12, postoperative: 0.78 +/- 0.28 (mean +/- 1 SD)--the SBF decreased by 50% (p less than 0.001) following reconstructive vascular surgery during day activities. During sleep, however, SBF increased by 80% (p less than 0.001). The relative changes in SBF from day to night at the postoperative examination did not differ from that of the control group, i.e., the normal 24-hour blood flow pattern had been obtained. These changes in SBF are explained by the reappearance of peripheral vasoregulatory mechanisms. Postreconstructive hyperemia was evaluated by the same technique. The changes in SBF following surgery in the positions supine, awake and supine, asleep were found to be insignificant (0.80 less than p less than 0.90). It is concluded that the long-term postreconstructive hyperemia merely is a reflection of the normal 24-hour blood flow pattern.

  20. Damage of vascular endothelial barrier induced by explosive blast and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Wang; Jing Chen

    2016-01-01

    In recent years,injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities.Tear.bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage.Vascular endothelial barrier is the main defense of tissues and organs' integrity.This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier,blood-air barrier,and intestinal vascular barrier impairments.In addition,the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast.

  1. Blood flow measurements during hemodialysis vascular access interventions - Catheter-based thermodilution or Doppler ultrasound?

    DEFF Research Database (Denmark)

    Heerwagen, Søren T; Hansen, Marc A; Schroeder, Torben V

    2012-01-01

    Purpose: To test the clinical performance of catheter-based thermodilution and Doppler ultrasound of the feeding brachial artery for blood flow measurements during hemodialysis vascular access interventions.Methods: Thirty patients with arteriovenous fistulas who underwent 46 interventions had...... by ultrasound dilution was determined within three days of the procedure. The methods were compared using regression analysis and tested for systematic bias. Results: Failure to position the thermodilutional catheter correctly was observed in 8 out of 46 (17%) pre-intervention measurements. Post...

  2. l-Homocysteine-induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia.

    Science.gov (United States)

    Leng, Yi-Ping; Ma, Ye-Shuo; Li, Xiao-Gang; Chen, Rui-Fang; Zeng, Ping-Yu; Li, Xiao-Hui; Qiu, Cheng-Feng; Li, Ya-Pei; Zhang, Zhen; Chen, Alex F

    2017-06-20

    Vascular inflammation, including the expression of inflammatory cytokines in endothelial cells, plays a critical role in hyperhomocysteinaemia-associated vascular diseases. Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on l-homocysteine-induced vascular inflammation. A high methionine diet-induced hyperhomocysteinaemic mouse model was used to assess cathepsin V expression and vascular inflammation. Cultures of HUVECs were challenged with l-homocysteine and the cathepsin L/V inhibitor SID to assess the pro-inflammatory effects of cathepsin V. Transfection and antisense techniques were utilized to investigate the effects of cathepsin V on the dual-specificity protein phosphatases (DUSPs) and MAPK pathways. Cathepsin L (human cathepsin V homologous) was increased in the thoracic aorta endothelial cells of hyperhomocysteinaemic mice; l-homocysteine promoted cathepsin V expression in HUVECs. SID suppressed the activity of cathepsin V and reversed the up-regulation of inflammatory cytokines (IL-6, IL-8 and TNF-α), adhesion and chemotaxis of leukocytes and vascular inflammation induced by l-homocysteine in vivo and in vitro. Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1/2, phosphorylation of STAT1 and expression of IL-6, IL-8 and TNF-α. This study has identified a novel mechanism, which shows that l-homocysteine-induced upregulation of cathepsin V mediates vascular endothelial inflammation under high homocysteine condition partly via ERK1/2 /STAT1 pathway. This mechanism could represent a potential therapeutic target in hyperaemia-associated vascular diseases. © 2017 The British Pharmacological Society.

  3. Forearm skin tissue dielectric constant measured at 300 MHz: effect of changes in skin vascular volume and blood flow.

    Science.gov (United States)

    Mayrovitz, Harvey N; Guo, Xiaoran; Salmon, Mark; Uhde, Matt

    2013-01-01

    Skin tissue dielectric constant (TDC) values measured via the open-ended coaxial probe method are useful non-invasive indices of local skin tissue water. However, the effect of skin blood flow (SBF) or skin blood volume (SBV) on TDC values is unknown. To determine the magnitude of such effects, we decreased forearm SBV via vertical arm raising for 5 min (test 1) and increased SBV by bicep cuff compression to 50 mmHg for 5 min (test 2) in 20 healthy supine subjects (10 men). TDC values were measured to a depth of 1·5 mm on anterior forearm, and SBF was measured with laser-Doppler system simultaneously on forearm and finger. Results indicate that decreasing vascular volume (test 1) was associated with a small but statistically significant reduction in TDC (3·0 ± 4·3%, P = 0·003) and increasing vascular volume (test 2) was associated with a slight but statistically significant increase in TDC (3·5 ± 3·0%, PTDC values (3·0-3·5%) over the wide range of induced SBV and SBF changes suggest a minor effect on clinically determined TDC values because of SBV or SBF changes or differences when comparing TDC longitudinally over time or among individuals of different groups in a research setting.

  4. Real-time Doppler-based arterial vascular impedance and peripheral pressure-flow loops: a pilot study.

    Science.gov (United States)

    Thiele, Robert H; Bartels, Karsten; Esper, Stephen; Ikeda, Keita; Gan, Tong-Joo

    2014-02-01

    Arterial pressure-flow loops and vascular impedance provide additional data that could be used to assess the hemodynamic effects of therapeutic interventions in anesthetized patients. To evaluate the utility of such an approach, the authors sought to design a device that combines flow waveforms from an esophageal Doppler probe and pressure waveforms from a peripheral artery to produce real-time pressure-flow loops and estimates of arterial vascular impedance. Prospective, cohort study. Single center, university-based teaching hospital. Patients undergoing surgery in whom the attending anesthesiologist had opted to place an esophageal Doppler probe and a peripheral arterial catheter for hemodynamic monitoring. This was a non-interventional study designed to record pressure-flow loops and arterial vascular impedance intraoperatively using a novel, noninvasive device. Pressure-flow loops and arterial vascular impedance were measured noninvasively using radial artery pressure and descending thoracic aorta flow waveforms in real time. Real-time arterial vascular impedance and peripheral pressure-volume loops can be determined using available monitoring devices. Technical feasibility of this technology in patients is a crucial first step to permit meaningful evaluation of the clinical value of this approach for accurate determination of complex hemodynamic indices and, eventually, improvement of outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Statins inhibited erythropoietin-induced proliferation of rat vascular smooth muscle cells.

    Science.gov (United States)

    Kaneda, Tae; Tsuruoka, Shuichi; Fujimura, Akio

    2010-12-15

    Erythropoietin (EPO) directly stimulates the proliferation of vascular smooth muscle cells, and this is believed to be one of the mechanisms of vascular access failure of hemodialysis patients. However, precise mechanisms of the EPO-induced proliferation of vascular smooth muscle cells are not certain. HMG-CoA reductase inhibitors (statins) are primarily used to reduce cholesterol levels, but also exert other effects, including reno-protective effects. We evaluated the effect of several statins with various hydrophilicities on the EPO-induced proliferation of primary cultured rat vascular smooth muscle cells (VSMCs) in vitro. EPO significantly and concentration-dependently increased DNA synthesis as assessed by [³H]thymidine incorporation, cell proliferation as assessed by WST-1 assay, and activation of the p44/42MAPK pathway. Therapeutic doses of statins (pravastatin, simvastatin, atorvastatin and fluvastatin) in patients with hypercholesterolemia almost completely suppressed all of the EPO-induced effects in a concentration-dependent manner. Co-addition of mevalonic acid almost completely reversed the effects of statins. Statin alone did not affect the basal proliferation capacity of the cells. The effects were almost similar among the statins. We concluded that statins inhibited EPO-induced proliferation in rat VSMCs at least partly through their inhibition of HMG-CoA reductase activity. In the future, statins might prove useful for the treatment of EPO-induced hyperplasia of vascular access. Because the statins all showed comparable effects irrespective of their hydrophilicities, these effects might be a class effect.

  6. Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

    Directory of Open Access Journals (Sweden)

    Upa Kukongviriyapan

    2014-03-01

    Full Text Available Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L in drinking water for eight weeks. Curcumin (50 or 100 mg/kg was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.

  7. In Vitro Model of Physiological and Pathological Blood Flow with Application to Investigations of Vascular Cell Remodeling.

    Science.gov (United States)

    Elliott, Winston; Scott-Drechsel, Devon; Tan, Wei

    2015-11-03

    Vascular disease is a common cause of death within the United States. Herein, we present a method to examine the contribution of flow dynamics towards vascular disease pathologies. Unhealthy arteries often present with wall stiffening, scarring, or partial stenosis which may all affect fluid flow rates, and the magnitude of pulsatile flow, or pulsatility index. Replication of various flow conditions is the result of tuning a flow pressure damping chamber downstream of a blood pump. Introduction of air within a closed flow system allows for a compressible medium to absorb pulsatile pressure from the pump, and therefore vary the pulsatility index. The method described herein is simply reproduced, with highly controllable input, and easily measurable results. Some limitations are recreation of the complex physiological pulse waveform, which is only approximated by the system. Endothelial cells, smooth muscle cells, and fibroblasts are affected by the blood flow through the artery. The dynamic component of blood flow is determined by the cardiac output and arterial wall compliance. Vascular cell mechano-transduction of flow dynamics may trigger cytokine release and cross-talk between cell types within the artery. Co-culture of vascular cells is a more accurate picture reflecting cell-cell interaction on the blood vessel wall and vascular response to mechanical signaling. Contribution of flow dynamics, including the cell response to the dynamic and mean (or steady) components of flow, is therefore an important metric in determining disease pathology and treatment efficacy. Through introducing an in vitro co-culture model and pressure damping downstream of blood pump which produces simulated cardiac output, various arterial disease pathologies may be investigated.

  8. Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Chakkarwar, Vishal Arvind

    2011-01-01

    The study has been designed to investigate the effect of fenofibrate on nicotine-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) was administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy of thoracic aorta. The expression of mRNA for p22phox and eNOS was assessed by using reverse transcriptase-polymerase chain reaction. Serum thiobarbituric acid reactive substances concentration (TBARS) and aortic superoxide anion concentration were estimated to assess oxidative stress. Moreover, the serum lipid profile was assessed by estimating serum cholesterol, triglycerides and high density lipoprotein. The administration of nicotine induces VED by increased oxidative stress, altered lipid profile and impaired the integrity of vascular endothelium as assessed in terms of decrease in expression of mRNA for endothelial nitric oxide synthase (eNOS), impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine produced oxidative stress, assessed in terms of increase in serum TBARS and aortic superoxide anion generation and increase in expression of mRNA for p22phox. Nicotine altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. However, treatment with fenofibrate (32 mg/kg, p.o.) markedly prevented nicotine-induced VED by decreasing oxidative stress and improving integrity of vascular endothelium, normalising the altered lipid profile, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic

  9. klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes.

    Directory of Open Access Journals (Sweden)

    Peter Novodvorsky

    Full Text Available The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2 transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development.Using Transcription Activator-Like Effector Nucleases (TALEN we generated a klf2a mutant (klf2ash317 with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl, a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17 in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants.The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development.

  10. Adventitial gene transfer of catalase attenuates angiotensin II-induced vascular remodeling.

    Science.gov (United States)

    Liu, Cun-Fei; Zhang, Jia; Shen, Kai; Gao, Ping-Jin; Wang, Hai-Ya; Jin, Xin; Meng, Chao; Fang, Ning-Yuan

    2015-04-01

    Vascular adventitia and adventitia‑derived reactive oxygen species (ROS) contribute to vascular remodeling following vascular injury. A previous ex vivo study in adventitial fibroblasts showed that catalase, one of most important anti‑oxide enzymes, was downregulated by angiotensin II (AngII). The aim of the present study was to investigate whether adventitial gene transfer of catalase affects AngII‑induced vascular remodeling in vivo. Adenoviruses co‑expressing catalase and enhanced green fluorescent protein (eGFP) or expressing eGFP only were applied to the adventitial surface of common carotid arteries of Sprague‑Dawley rats. Alzet minipumps administering AngII (0.75 mg/kg/day) were then implanted subcutaneously for 14 days. Systolic blood pressure and biological parameters of vascular remodeling were measured in each group. Adventitial fibroblasts were cultured and p38 mitogen‑activated protein kinase (MAPK) phosphorylation was measured using western blot analysis. The results showed that adventitial gene transfer of catalase had no effect on AngII‑induced systolic blood pressure elevation. However, catalase adenovirus transfection significantly inhibited AngII‑induced media hypertrophy compared with that of the control virus (Pcatalase transfection significantly attenuated AngII‑induced ROS generation, macrophage infiltration, collagen deposition and adventitial α‑smooth muscle actin expression. Furthermore, catalase transfection significantly inhibited the AngII‑induced increase in p38MAPK phosphorylation. In conclusion, the results of the present study demonstrated that adventitial gene transfer of catalase significantly attenuated AngII‑induced vascular remodeling in rats via inhibition of adventitial p38MAPK phosphorylation.

  11. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  12. miRNA-146a induces vascular smooth muscle cell apoptosis in a rat model of coronary heart disease via NF-κB pathway.

    Science.gov (United States)

    Wu, Z W; Liu, Y F; Wang, S; Li, B

    2015-12-29

    The aim of this study was to investigate the role of miRNA-146a in modulating the function of vascular smooth muscle cells in a rat model of coronary heart disease. Vascular smooth muscle cells were isolated and cultured from the rat coronary heart disease model and normal rats (controls). miRNA-146a levels were measured in vascular smooth muscle cells obtained from rats with coronary heart disease and control rats. The proliferation, growth, apoptosis, and activation of the NF-κB pathway in the vascular smooth muscle cells were detected using the MTT assay and flow cytometry, respectively. The role of the NF-κB pathway in modulating the apoptosis of vascular smooth muscle cells was investigated by measuring the reactivity of the cells to an NF-κB pathway inhibitor (TPCA-1). Vascular smooth muscle cells from the disease model exhibited higher levels of miRNA-146a than that by the normal controls (P = 0.0024). The vascular smooth muscle cells obtained from rats with coronary heart disease showed decreased proliferation and growth and increased apoptosis. miRNA-146a overexpression elevated the rate of cell apoptosis. The NF-κB pathway was activated in vascular smooth muscle cells obtained from rats with coronary heart disease. Inhibition of the NF- κB pathway significantly decreased the rate of vascular smooth muscle cell apoptosis in coronary heart disease rats (P = 0.0038). In conclusion, miRNA- 146a was found to induce vascular smooth muscle cell apoptosis in rats with coronary heart disease via the activation of the NF-κB signal pathway.

  13. Vascular flow density in pathological myopia: an optical coherence tomography angiography study.

    Science.gov (United States)

    Mo, Jing; Duan, Anli; Chan, Szyyann; Wang, Xuefei; Wei, Wenbin

    2017-02-03

    To investigate vascular flow density in pathological myopia with optical coherence tomography (OCT) angiography. A prospective comparative study was conducted from December 2015 to March 2016. Participants were recruited in Beijing Tongren Hospital. A total of 131 eyes were enrolled, which were divided into three groups: 45 eyes with emmetropia (EM; mean spherical equivalent (MSE) 0.50D to -0.50D), 41 eyes with high myopia (HM; MSE ≤-6.00D, without pathological changes), and 45 eyes with pathological myopia (PM; MSE ≤-6.00D and axial length (AL) ≥26.5 mm, and with pathological changes). Macular, choriocapillaris and radial peripapillary capillary (RPC) flow densities were measured and compared between groups, and their relationships with AL and best corrected visual acuity (BCVA) were analysed. Significant differences were found in macular, choriocapillaris and RPC flow densities among the three groups (pdensities of the PM group were significantly decreased (pdensity was found between the PM and HM groups (p=0.731). Compared with the EM group, retinal flow density in the macular and arcuate fibre region was not decreased in the HM group. In addition, there was a negative correlation between AL and superficial macular flow density (β=-0.542, pdensity (β=-0.282, p=0.002) and RPC flow density (β=-0.522, pdensity (β=0.194, p=0.021), deep macular flow density (β=0.373, pdensity (β=0.291, p=0.001). Macular and RPC flow densities decreased in pathological myopia compared with high myopia and emmetropia. No significant decrease of retinal flow density in the macular and arcuate fibre region was found in high myopic eyes compared with emmetropic eyes. Moreover, macular and RPC flow densities were negatively related to AL, and macular flow density was positively related to BCVA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. RETINAL BLOOD FLOW CORRELATES TO AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR IN CENTRAL RETINAL VEIN OCCLUSION.

    Science.gov (United States)

    Yamada, Yoshihisa; Suzuma, Kiyoshi; Matsumoto, Makiko; Tsuiki, Eiko; Fujikawa, Azusa; Harada, Takafumi; Kitaoka, Takashi

    2015-10-01

    As laser speckle flowgraphy can measure blood flow distribution in the ocular fundus, the authors analyzed the relationship between retinal blood flow and aqueous vascular endothelial growth factor (VEGF) concentration in central retinal vein occlusion. This prospective observational study examined 45 eyes of 45 patients with central retinal vein occlusion before treatment. Blood flow in large vessels around and at the optic disk, aqueous VEGF concentration, and arteriovenous passage time were examined. Blood flow was evaluated as mean blur rate by laser speckle flowgraphy. Fluorescein angiography found 20 ischemic and 25 nonischemic type eyes. Aqueous VEGF concentration in the ischemic type was significantly higher than that in the nonischemic type (P = 0.01). Arteriovenous passage time was significantly correlated to the logarithm of the aqueous VEGF concentration (P = 0.0001). Mean blur rate of the affected eye/mean blur rate of the unaffected eye of the ischemic type was significantly lower than the nonischemic type (P = 0.039). Additionally, mean blur rate was significantly correlated both to the logarithm of the aqueous VEGF concentration (P central retinal vein occlusion.

  15. Evaluation of flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells

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    Inoue, Yusuke; Yoshikawa, Kohki; Yoshioka, Naoki; Ohtake, Tohru; Ohtomo, Kuni [Tokyo Univ. (Japan). Dept. of Radiology; Wakita, Shinichi; Kaji, Nobuyuki; Harii, Kiyonori [Dept. of Plastic Surgery, Univ. of Tokyo (Japan)

    1999-04-29

    The estimation of intralesional haemodynamics is crucial in determining appropriate treatment for soft-tissue vascular malformations. The aim of this study was to develop a method to evaluate the flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells ({sup 99m}Tc-RBCs). Seventy-nine soft-tissue vascular malformations, including 20 arteriovenous malformations and 59 venous malformations, in 57 patients were examined. Following the intravenous injection of {sup 99m}Tc-RBCs, dynamic imaging was performed for 30 min with the lesion in the field of view ({sup 99m}Tc-RBC flow study). A time-activity curve was generated for the lesion, and the lesion was categorized as a high-flow or low-flow lesion by visual inspection of the curve. In low-flow lesions, mean vascular transit time (MTT) was calculated by curve fitting based on a two-compartment model. Twenty-nine lesions in 19 patients were examined twice, and reproducibility was assessed. In 23 venous malformations in 16 patients, {sup 99m}Tc-Sn colloid was percutaneously injected into the intravascular space of the lesion, and dynamic data of 5-min duration were acquired (direct puncture scintigraphy). MTT was estimated from the washout curve and compared with MTT estimated by {sup 99m}Tc-RBC flow study. {sup 99m}Tc-RBC flow study classified all 20 arteriovenous malformations as high-flow lesions and all 59 venous malformations as low-flow lesions. In the low-flow lesions, MTT estimated by {sup 99m}Tc-RBC flow study ranged from 61.2 to 2174.9 s. In the reproducibility study, complete concordance in classification and high correlation in MTT were shown between the first and second examinations. MTT estimated by {sup 99m}Tc-RBC flow study was significantly correlated with that estimated by direct puncture scintigraphy. In summary, {sup 99m}Tc-RBC flow study provides a quantitative indicator of intralesional haemodynamics in low-flow lesions in addition to accurate

  16. Deformation mechanism of leukocyte adhering to vascular surface under steady shear flow

    Institute of Scientific and Technical Information of China (English)

    LIU; Xiaoheng; WANG; Xiong; YIN; Hongmei; CHEN; Huaiqing

    2004-01-01

    The adhesion of leukocytes to vascular surface is an important biomedical problem and has drawn extensive attention. In this study, we propose a compound drop model to simulate a leukocyte with a nucleus adhering to the surface of blood vessel under steady shear flow. A two-dimensional computational fluid dynamics (CFD) is conducted to determine the local distribution of pressure on the surface of the adherent model cell. By introducing the parameter of deformation index (DI), we investigate the deformation of the leukocyte and its nucleus under controlled conditions. Our numerical results show that: (i) the leukocyte is capable of deformation under external exposed flow field. The deformation index increases with initial contact angle and Reynolds number of external exposed flow. (ii) The nucleus deforms with the cell, and the deformation index of the leukocyte is greater than that of the nucleus. The leukocyte is more deformable while the nucleus is more capable of resisting external shear flow. (iii) The leukocyte and the nucleus are not able to deform infinitely with the increase of Reynolds number because the deformation index reaches a maximum. (iv) Pressure distribution confirms that there exists a region downstream of the cell, which produces high pressure to retard continuous deformation and provide a positive lift force on the cell. Meanwhile, we have measured the deformation of human leukocytes exposed to shear flow by using a flow chamber system. We found that the numerical results are well consistent with those of experiment. We conclude that the nucleus with high viscosity plays a particular role in leukocyte deformation.

  17. Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Topal, Gökçe; Koç, Ebru; Karaca, Cetin; Altuğ, Tuncay; Ergin, Bülent; Demirci, Cihan; Melikoğlu, Gülay; Meriçli, Ali H; Kucur, Mine; Ozdemir, Osman; Uydeş Doğan, B Sönmez

    2013-03-01

    Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)  M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation. Copyright © 2012 John Wiley & Sons, Ltd.

  18. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock.

    Science.gov (United States)

    Mikelis, Constantinos M; Simaan, May; Ando, Koji; Fukuhara, Shigetomo; Sakurai, Atsuko; Amornphimoltham, Panomwat; Masedunskas, Andrius; Weigert, Roberto; Chavakis, Triantafyllos; Adams, Ralf H; Offermanns, Stefan; Mochizuki, Naoki; Zheng, Yi; Gutkind, J Silvio

    2015-04-10

    Histamine-induced vascular leakage is an integral component of many highly prevalent human diseases, including allergies, asthma and anaphylaxis. Yet, how histamine induces the disruption of the endothelial barrier is not well defined. By using genetically modified animal models, pharmacologic inhibitors and a synthetic biology approach, here we show that the small GTPase RhoA mediates histamine-induced vascular leakage. Histamine causes the rapid formation of focal adherens junctions, disrupting the endothelial barrier by acting on H1R Gαq-coupled receptors, which is blunted in endothelial Gαq/11 KO mice. Interfering with RhoA and ROCK function abolishes endothelial permeability, while phospholipase Cβ plays a limited role. Moreover, endothelial-specific RhoA gene deletion prevents vascular leakage and passive cutaneous anaphylaxis in vivo, and ROCK inhibitors protect from lethal systemic anaphylaxis. This study supports a key role for the RhoA signalling circuitry in vascular permeability, thereby identifying novel pharmacological targets for many human diseases characterized by aberrant vascular leakage.

  19. Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility.

    Science.gov (United States)

    Je, Hyun Dong; Sohn, Uy Dong; La, Hyen-Oh

    2016-01-01

    Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.

  20. SDF-1 promotes ox-LDL induced vascular smooth muscle cell proliferation.

    Science.gov (United States)

    Li, Ling-Xing; Zhang, Xian-Feng; Bai, Xue; Tong, Qian

    2013-09-01

    The mechanism of the regulatory roles of stromal cell derived factor-1 (SDF-1)/C-X-C motif receptor 4 (CXCR4) on cell proliferation and apoptosis in vascular smooth muscle cells (VSMCs) via the protein kinase C (PKC) and nuclear factor-kappa B (NF-κB) signalling pathways have been investigated. Rat aortic VSMCs were treated with control or an oxidised low-density lipoprotein (ox-LDL) atherosclerosis (AS) model. Cells exposed to the AS model were treated with SDF-1 plus inhibitors specific for PKC (Ro31-8220), CXCR4 (12G5) or NF-κB (pyrrolidine dithiocarbamate, PDTC). Cell proliferation was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis by flow cytometry. NF-κB protein expression was analysed using Western blotting. The proliferation rate in the AS model group was significantly higher than the control group, but lower than the SDF-1 group (P SDF-1 group was significantly lower than the normal control group (P SDF-1 group was significantly higher than the AS model (ox-LDL) group (P SDF-1 can promote the proliferation of VSMCs induced by ox-LDL and inhibit cell apoptosis, via the SDF-1/CXCR4 axis.

  1. Hydroxysafflor yellow A suppresses oxidized low density lipoprotein induced proliferation of vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Lin Sheng

    2012-06-01

    Full Text Available To investigate the relationship between the suppression of Hydroxysafflor yellow A (HSYA on the oxidized low density lipoprotein (ox-LDL induced proliferation of vascular smooth muscle cells (VSMCs and the mRNA and protein expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2 and mitogen activated protein kinase phospholipase-1 (MAKP-1, VSMCs were treated with HSYA at 10 ?mol/L and/or ox-LDL at 35 mg/L for 48 h. MTT assay was done to measure cell survival rate, flow cytometry to detect cell cycle, reverse transcription PCR and Western blot to detect the expression of ERK1/2 and MAKP-1. When compared to cells treated with ox-LDL alone, the survival rate of cells treated with two reagents was reduced and the proportion of cells in G0/G1 phase significantly increased, with increased MKP-1 expression. The study suggests HSYA can inhibit VSMC proliferation via increasing MKP-1 expression, reducing p-ERK1/2 activity and suppressing cell cycle.

  2. E-Cigarette Aerosol Exposure Induces Reactive Oxygen Species, DNA Damage, and Cell Death in Vascular Endothelial Cells.

    Science.gov (United States)

    Anderson, Chastain; Majeste, Andrew; Hanus, Jakub; Wang, Shusheng

    2016-12-01

    Cigarette smoking remains one of the leading causes of preventable death worldwide. Vascular cell death and dysfunction is a central or exacerbating component in the majority of cigarette smoking related pathologies. The recent development of the electronic nicotine delivery systems known as e-cigarettes provides an alternative to conventional cigarette smoking; however, the potential vascular health risks of e-cigarette use remain unclear. This study evaluates the effects of e-cigarette aerosol extract (EAE) and conventional cigarette smoke extract (CSE) on human umbilical vein endothelial cells (HUVECs). A laboratory apparatus was designed to produce extracts from e-cigarettes and conventional cigarettes according to established protocols for cigarette smoking. EAE or conventional CSE was applied to human vascular endothelial cells for 4-72 h, dependent on the assay. Treated cells were assayed for reactive oxygen species, DNA damage, cell viability, and markers of programmed cell death pathways. Additionally, the anti-oxidants α-tocopherol and n-acetyl-l-cysteine were used to attempt to rescue e-cigarette induced cell death. Our results indicate that e-cigarette aerosol is capable of inducing reactive oxygen species, causing DNA damage, and significantly reducing cell viability in a concentration dependent fashion. Immunofluorescent and flow cytometry analysis indicate that both the apoptosis and programmed necrosis pathways are triggered by e-cigarette aerosol treatment. Additionally, anti-oxidant treatment provides a partial rescue of the induced cell death, indicating that reactive oxygen species play a causal role in e-cigarette induced cytotoxicity.

  3. Numerical Simulation of Steady and Pulsatile Flow Through Vascular Stenoses and Comparisons with Experiments Using Phase Contrast Magnetic Resonance Imaging

    Science.gov (United States)

    Behrens, Geoffrey; Agarwal, Ramesh; Moghaddam, Abbas N.; Choi, Eric T.; Amini, Amir A.

    2003-11-01

    A commercially available numerical flow solver "FLUENT" is employed in simulation of blood flow through vascular stenoses. Fluid properties are set to match those of the blood mimicking fluid used in flow phantom experiments at the Washington University School of Medicine. Computational results are compared for steady flow through axisymmetric and three-dimensional phantoms modeling mild to severe stenonses with the data collected using Phase Contrast Magnetic Resonance Imaging (PC-MRI) technique by colleagues in the CVIA laboratory at Washington University School of Medicine. Computations are also performed for pulsatile flow through vascular stenoses. Comparisons of PC-MRI and FLUENT output data show qualitative agreement in streamline patterns and good quantitative agreement for pressure drop across the stenoses.

  4. Flow-induced crystallization in isotactic polypropylene

    Science.gov (United States)

    Hamad, Fawzi Ghassan

    Brief intervals of strong flow stretch chains in a semicrystalline polymer melt, which results in an increase in the nuclei number density and a transformation of the crystal structure. This flow-induced crystallization (FIC) phenomenon is explored in this study using highly isotactic polypropylene (iPP) samples. Using one synthesized and five commercial linear isotactic polypropylene samples, we investigate the FIC behavior by imposing shear onto these samples in a rotational rheometer. Equipped with a good temperature control and flexible shear protocol, we apply different temperature and flow conditions. The magnitude of the FIC effect varies with basic processing parameters (shear rate, specific work, crystallization temperature, and shearing temperature) and material properties (totalistic, molecular weight distribution, and particle concentration in the polymer). The scope of this study is to systematically investigate the influences of these parameters on FIC. The FIC effects that are investigated in this dissertation are: crystallization kinetics, persistence time of flow-induced nuclei, and crystal morphology. The crystallization time was measured in the rheometer by monitoring the onset of crystallization after quenching samples sheared above Tm. These samples were subsequently used to study their flow-induced nuclei persistence time and crystal morphology. The lifetime of flow-induced nuclei was determined by measuring the time required to return from FIC back to quiescent crystallization using a differential scanning calorimeter. The crystal morphology was imaged using polarized optical microscopy and atomic force microscopy. We investigated the influence of specific work on the three FIC characteristics, and found three regimes that are separated by the critical work ( Wc) and the saturation work (Wsat) thresholds. Below the critical work threshold, the morphology is composed of mostly spherulite crystals, which keep a constant volume, and a small

  5. Cadmium induces vascular permeability via activation of the p38 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Fengyun [Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China); Guo, Fang [Department of Cardiology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021 (China); Li, Liqun [Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China); Guo, Ling; Hou, Yinglong; Hao, Enkui; Yan, Suhua [Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China); Allen, Thaddeus D. [G.W. Hooper Research Foundation, University of California at San Francisco, 513 Parnassus Ave., HSW1501, San Francisco, CA 94143-0552 (United States); Liu, Ju, E-mail: ju.liu@sdu.edu.cn [Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China)

    2014-07-18

    Highlights: • Low-dose cadmium (Cd) induces vascular hyper-permeability. • p38 MAPK mediates Cd-induced disruption of endothelial cell barrier function. • SB203850 inhibits Cd-induced membrane dissociation of VE-cadherin and β-catenin. • SB203850 reduces Cd-induced expression and secretion of TNF-α. - Abstract: The vasculature of various organs is a targeted by the environmental toxin, cadmium (Cd). However, mechanisms leading to pathological conditions are poorly understood. In the present study, we examined the effect of cadmium chloride (CdCl{sub 2}) on human umbilical vein endothelial cells (HUVECs). At 4 μM, CdCl{sub 2} induced a hyper-permeability defect in HUVECs, but not the inhibition of cell growth up to 24 h. This effect of CdCl{sub 2} was dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The p38 MAPK inhibitor SB203850 suppressed the CdCl{sub 2}-induced alteration in trans-endothelial electrical resistance in HUVEC monolayers, a model measurement of vascular endothelial barrier integrity. SB203850 also inhibited the Cd-induced membrane dissociation of vascular endothelial (VE) cadherin and β-catenin, the important components of the adherens junctional complex. In addition, SB203850 reduces the Cd-induced expression and secretion of tumor necrosis factor α (TNF-α). Taken together, our findings suggest that Cd induces vascular hyper-permeability and disruption of endothelial barrier integrity through stimulation of p38 MAPK signaling.

  6. Mitigation of Radiation Induced Pulmonary Vascular Injury by Delayed Treatment with Captopril

    Science.gov (United States)

    MOLTHEN, Robert C.; WU, Qingping; FISH, Brian L.; MOULDER, John E.; JACOBS, Elizabeth R.; MEDHORA, Meetha M.

    2013-01-01

    Background and objective A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2-months post-exposure. In this study we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2-months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2-weeks after radiation exposure, with 2 doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary hemodynamics, lung ACE activity, pulmonary arterial distensibility, and peripheral vessel density. Results Captopril, given at a vasoactive but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly these beneficial effects were observed even if drug therapy was delayed for up to two weeks after exposure. Conclusions Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident. PMID:22882664

  7. Tree mortality predicted from drought-induced vascular damage

    Science.gov (United States)

    Anderegg, William R. L.; Flint, Alan L.; Huang, Cho-ying; Flint, Lorraine E.; Berry, Joseph A.; Davis, Frank W.; Sperry, John S.; Field, Christopher B.

    2015-01-01

    The projected responses of forest ecosystems to warming and drying associated with twenty-first-century climate change vary widely from resiliency to widespread tree mortality1, 2, 3. Current vegetation models lack the ability to account for mortality of overstorey trees during extreme drought owing to uncertainties in mechanisms and thresholds causing mortality4, 5. Here we assess the causes of tree mortality, using field measurements of branch hydraulic conductivity during ongoing mortality in Populus tremuloides in the southwestern United States and a detailed plant hydraulics model. We identify a lethal plant water stress threshold that corresponds with a loss of vascular transport capacity from air entry into the xylem. We then use this hydraulic-based threshold to simulate forest dieback during historical drought, and compare predictions against three independent mortality data sets. The hydraulic threshold predicted with 75% accuracy regional patterns of tree mortality as found in field plots and mortality maps derived from Landsat imagery. In a high-emissions scenario, climate models project that drought stress will exceed the observed mortality threshold in the southwestern United States by the 2050s. Our approach provides a powerful and tractable way of incorporating tree mortality into vegetation models to resolve uncertainty over the fate of forest ecosystems in a changing climate.

  8. Chronic central vascular expansion induces hypokalemia in conscious primates

    Science.gov (United States)

    Moore-Ede, M. C.; Kass, D. A.

    1982-01-01

    Central vascular expansion maintained for four days in conscious squirrel monkeys reconciles the apparently conflicting short-term fluid and electrolyte responses to water immersion and atrial balloon distension, with those described for prolonged weightlessness during space flight. The monkeys are subjected to an increased lower body positive air pressure (LBPP) of 20 torr which produces a 3 cm water increase in the central venous pressure. Results show a marked increase in the urinary excretion of sodium, potassium, and water during the firxt six hours of LBPP, and the diuresis is maintained throughout the period of LBPP, although the levels of sodium and potassium excretion decline after 24 hours of exposure. Plasma aldosterone transiently drops within the first three hours of LBPP, and then regains normal levels within 24 hours, after which time these levels are maintained despite the continued LBPP stimulus. It is suggested that the normal plasma aldosterone levels observed in the experiments, as well as during space flight, might, epresent a relative hyposecretion in terms of volume homeostasis and a relative hypersecretion with respect to plasma potassium regulation. Thus, kaliuresis and marked natriuresis is confined primarly to the first 24 hours of central volume expansion, a period for which comparable data from space flights are lacking.

  9. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    Science.gov (United States)

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  10. Mechanical Stress Induces Remodeling of Vascular Networks in Growing Leaves.

    Directory of Open Access Journals (Sweden)

    Yohai Bar-Sinai

    2016-04-01

    Full Text Available Differentiation into well-defined patterns and tissue growth are recognized as key processes in organismal development. However, it is unclear whether patterns are passively, homogeneously dilated by growth or whether they remodel during tissue expansion. Leaf vascular networks are well-fitted to investigate this issue, since leaves are approximately two-dimensional and grow manyfold in size. Here we study experimentally and computationally how vein patterns affect growth. We first model the growing vasculature as a network of viscoelastic rods and consider its response to external mechanical stress. We use the so-called texture tensor to quantify the local network geometry and reveal that growth is heterogeneous, resembling non-affine deformations in composite materials. We then apply mechanical forces to growing leaves after veins have differentiated, which respond by anisotropic growth and reorientation of the network in the direction of external stress. External mechanical stress appears to make growth more homogeneous, in contrast with the model with viscoelastic rods. However, we reconcile the model with experimental data by incorporating randomness in rod thickness and a threshold in the rod growth law, making the rods viscoelastoplastic. Altogether, we show that the higher stiffness of veins leads to their reorientation along external forces, along with a reduction in growth heterogeneity. This process may lead to the reinforcement of leaves against mechanical stress. More generally, our work contributes to a framework whereby growth and patterns are coordinated through the differences in mechanical properties between cell types.

  11. [The development of the system of blood flow block by using magnetic compression abdominal large vascular].

    Science.gov (United States)

    Yan, Xiaopeng; Lv, Yi; Ma, Feng; Ma, Jia; Wang, Haohua; Wang, Shanpei; Li, Dichen; Liu, Yaxiong; Jia, Shenli; Shi, Zongqian; Luo, Ruixue

    2014-03-01

    A new system of blood flow block for control of bleeding in abdominal operation is composed of an abdominal magnetic blocking unit, an abdominal external electromagnet unit and other non-magnetic operation instrument. The abdominal external electromagnetic unit is placed in advance in the operation bed. The abdominal magnetic blocking unit can be placed directly on the ventral of the large vessels when need to blocking the abdominal large vessels during the operation. According to the non-contact suction characteristics of magnetic materials, the two magnetic units will attract each other and compression the vessels. Using this system for vascular occlusion does not need clear exposure and without separating vessel. There is the advantage of rapid, accurate and reliable for the system.

  12. Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

    Science.gov (United States)

    Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

    2015-07-01

    Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed.

  13. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Directory of Open Access Journals (Sweden)

    Xue-ying Chang

    2017-01-01

    Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  14. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Al-Khazraji, Baraa K; Mortensen, Stefan P

    2013-01-01

    During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However......, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were...... studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 µM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition...

  15. Trans fatty acids induce vascular inflammation and reduce vascular nitric oxide production in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Naomi G Iwata

    Full Text Available Intake of trans fatty acids (TFA, which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived-dairy products and meat on endothelial NF-κB activation and nitric oxide (NO production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans, Linoelaidic (trans-C18:2 (9 trans, 12 trans, and Transvaccenic (trans-C18:1 (11 trans for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation.

  16. MicroRNA changes in rat mesentery and serum associated with drug-induced vascular injury

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Roberta A., E-mail: Roberta.A.Thomas@gsk.com; Scicchitano, Marshall S.; Mirabile, Rosanna C.; Chau, Nancy T.; Frazier, Kendall S.; Thomas, Heath C.

    2012-08-01

    Regulatory miRNAs play a role in vascular biology and are involved in biochemical and molecular pathways dysregulated during vascular injury. Collection and integration of functional miRNA data into these pathways can provide insight into pathogenesis at the site of injury; the same technologies applied to biofluids may provide diagnostic or surrogate biomarkers. miRNA was analyzed from mesentery and serum from rats given vasculotoxic compounds for 4 days. Fenoldopam, dopamine and midodrine each alter hemodynamics and are associated with histologic evidence of vascular injury, while yohimbine is vasoactive but does not cause histologic evidence of vascular injury in rat. There were 38 and 35 miRNAs altered in a statistically significant manner with a fold change of 2 or greater in mesenteries of fenoldopam- and dopamine-dosed rats, respectively, with 9 of these miRNAs shared. 10 miRNAs were altered in rats given midodrine; 6 were shared with either fenoldopam or dopamine. In situ hybridization demonstrated strong expression and co-localization of miR-134 in affected but not in adjacent unaffected vessels. Mesenteric miRNA expression may provide clarity or avenues of research into mechanisms involved in vascular injury once the functional role of specific miRNAs becomes better characterized. 102 miRNAs were altered in serum from rats with drug-induced vascular injury. 10 miRNAs were commonly altered in serum from dopamine and either fenoldopam or midodrine dosed rats; 18 of these 102 were also altered in mesenteries from rats with drug-induced vascular injury, suggesting their possible utility as peripheral biomarkers. -- Highlights: ► Mesentery and serum were examined from rats given vasoactive compounds for 4 days. ► 72 miRNAs were altered in mesenteries from rats with vascular injury. ► miR-134 was localized to affected but not adjacent unaffected vessels. ► 102 miRNAs were changed in serum from rats with vascular injury. ► 18 miRNAs changed in both

  17. Opioid-induced proliferation of vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Sandra Leo

    2009-05-01

    Full Text Available Sandra Leo1,2, Rony Nuydens1, Theo F Meert11Pain and Neurology, CNS Department, Johnson and Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica N.V, Beerse, Belgium; 2Laboratory of Biological Psychology, University of Leuven, Leuven, BelgiumAbstract: Angiogenesis is an important issue in cancer research and opioids are often used to treat pain in cancer patients. Therefore it is important to know if the use of opioids is associated with an aberrant stimulation of tumor growth triggered by the stimulation of angiogenesis in cancer patients. Some studies in the literature have suggested the presence of the μ3 opioid receptor, known as the receptor for many opioids, on endothelial cells, which are key players in the process of angiogenesis. In this study we used endothelial cells known to express the μ3 opioid receptor (MOR3, to evaluate the effects of morphine on angiogenesis. We first investigated the effect of morphine on the proliferation of endothelial cells. We showed that morphine is able to stimulate vascular endothelial cell proliferation in vitro. This effect of morphine is mediated by the mitogen-activated protein kinase (MAPK pathway as pre-treatment with PD98059 inhibited this excessive proliferation. Because previous studies indicated nitric oxide (NO as a downstream messenger we investigated the role of NO in the aberrant proliferation of endothelial cells. Our data could not confirm these findings using intracellular NO measurements and quantitative fluorescence microscopy. The potential use and pitfalls of opioids in cancer patients is discussed in light of these negative findings. Keywords: endothelial cells, morphine, cell proliferation, MAPK, nitric oxide, μ3 opioid receptor, angiogenesis

  18. Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability

    Directory of Open Access Journals (Sweden)

    Yun-Liang Cui

    2016-01-01

    Conclusions: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.

  19. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  20. Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling

    Directory of Open Access Journals (Sweden)

    Felty Quentin

    2006-04-01

    Full Text Available Abstract Background Since estrogen is known to increase vascular endothelial cell growth, elevated estrogen exposure from hormone replacement therapy or oral contraceptives has the potential to contribute in the development of abnormal proliferative vascular lesions and subsequent thickening of the vasculature. How estrogen may support or promote vascular lesions is not clear. We have examined in this study whether estrogen exposure to vascular endothelial cells increase the formation of reactive oxygen species (ROS, and estrogen-induced ROS is involved in the growth of endothelial cells. Methods The effect of estrogen on the production of intracellular oxidants and the role of estrogen-induced ROS on cell growth was studied in human umbilical vein endothelial cells. ROS were measured by monitoring the oxidation of 2'7'-dichlorofluorescin by spectrofluorometry. Endothelial cell growth was measured by a colorimetric immunoassay based on BrdU incorporation into DNA. Results Physiological concentrations of estrogen (367 fmol and 3.67 pmol triggered a rapid 2-fold increase in intracellular oxidants in endothelial cells. E2-induced ROS formation was inhibited to basal levels by cotreatment with the mitochondrial inhibitor rotenone (2 μM and xanthine oxidase inhibitor allopurinol (50 μM. Inhibitors of NAD(PH oxidase, apocynin and DPI, did not block E2-induced ROS formation. Furthermore, the NOS inhibitor, L-NAME, did not prevent the increase in E2-induced ROS. These findings indicate both mitochondria and xanthine oxidase are the source of ROS in estrogen treated vascular endothelial cells. E2 treated cells showed a 2-fold induction of BrdU incorporation at 18 h which was not observed in cells exposed to vehicle alone. Cotreatment with ebselen (20 μM and NAC (1 mM inhibited E2-induced BrdU incorporation without affecting the basal levels of DNA synthesis. The observed inhibitory effect of NAC and ebselen on E2-induced DNA synthesis was also shown

  1. Effect of Adrenomedullin on Pulmonary Vascular Structural Remodeling Induced by High Pulmonary Blood Flow in Rats%肾上腺髓质素对大鼠高肺血流性肺血管结构重构的干预作用

    Institute of Scientific and Technical Information of China (English)

    高扬; 齐建光; 李晓惠; 庞璐璐; 金红芳; 杜军保

    2012-01-01

    Objective To explore the effect of adrenomedullin ( ADM) on the pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by high pulmonary blood flow. Methods Twenty - one male 6 - week - old SD rats were randomly divided into control group (n = 7 ) , shunt group ( n = 7 ) and shunt with ADM group (n = 7). Aortocaval shunting was produced in rats of shunt group and shunt with ADM group. In control group,the inferior vena cava and abdominal aorta were only exposed,but shunting procedure was not performed. After 8 weeks,ADM (1. 5 μg · kg-1 · h-1) was subcutaneously administered into rats of shunt with ADM group by mini - osmotic pump for 2 weeks. Pulmonary artery pressures of each rat were evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass.[ RV/( LV + SP) ] was calculated after weighting. The pulmonary artery micro - and ultra - morphologic changes of rats were observed. Results Compared with the rats of control group,pulmonary artery systolic pressure,pulmonary artery diastolic pressure,pulmonary artery mean pressure and RV/( LV + SP) in rats of shunt group were significantly increased (Pa <0.01) ,the muscularization of small pulmonary vessels, relative medial thickness and relative medial area of the pulmonary arteries were also significantly increased (Pa <0. 01 ). Ultrastructural changes, including swelling of endothelial cells, irregularity of inner elastic lamina, and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells,were found in pulmonary arteries of shunting rats. Pulmonary artery pressure and RV/(LV +SP) in rats of shunt with ADM group were significantly decreased compared with those of shunt group (Pa <0.01) ,with the alleviation of pulmonary artery micro - and ultra - morphologic changes. Conclusions ADM subcutaneously administered by mimi - osmotic pump alleviated the development of pulmonary hypertension and

  2. Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells.

    Science.gov (United States)

    Ochi, Masanori; Kawai, Yoshiko; Tanaka, Yoshiyuki; Toyoda, Hiromu

    2015-02-01

    Nicardipine hydrochloride (NIC), a dihydropyridine calcium-channel blocking agent, has been widely used for the treatment of hypertension. Especially, nicardipine hydrochloride injection is used as first-line therapy for emergency treatment of abnormally high blood pressure. Although NIC has an attractive pharmacological profile, one of the dose-limiting factors of NIC is severe peripheral vascular injury after intravenous injection. The goal of this study was to better understand and thereby reduce NIC-mediated vascular injury. Here, we investigated the mechanism of NIC-induced vascular injury using human dermal microvascular endothelial cells (HMVECs). NIC decreased cell viability and increased percent of dead cells in a dose-dependent manner (10-30 μg/mL). Although cell membrane injury was not significant over 9 hr exposure, significant changes of cell morphology and increases in vacuoles in HMVECs were observed within 30 min of NIC exposure (30 μg/mL). Autophagosome labeling with monodansylcadaverine revealed increased autophagosomes in the NIC-treated cells, whereas caspase 3/7 activity was not increased in the NIC-treated cells (30 μg/mL). Additionally, NIC-induced reduction of cell viability was inhibited by 3-methyladenine, an inhibitor of autophagosome formation. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy could contribute to the reduction of NIC-induced vascular injury.

  3. Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

    Science.gov (United States)

    Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L; Connelly, Rhykka; Nakano, Yoshimitsu; Traber, Lillian D; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-11-01

    Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  4. Blood flow and vascular reactivity during attacks of classic migraine--limitations of the Xe-133 intraarterial technique

    DEFF Research Database (Denmark)

    Skyhøj Olsen, T; Lassen, N A

    1989-01-01

    The present study reports cerebral blood flow (CBF) measurements in 11 patients during attacks of classic migraine (CM)--migraine with aura. In 6 and 7 patients, respectively, cerebral vascular reactivity to increased blood pressure and to hypocapnia was also investigated during the CM attacks. T...

  5. Improved determination of vascular blood-flow shear rate using Doppler ultrasound

    Science.gov (United States)

    Farison, James B.; Begeman, Garett A.; Salles-Cunha, Sergio X.; Beebe, Hugh G.

    1997-05-01

    Shear rate has been linked to endothelial and smooth muscle cell function, neointimal hyperplasia, poststenotic dilation and progression of atherosclerotic plaque. In vivo studies of shear rate have been limited in humans due to the lack of a truly accurate noninvasive method of measuring blood flow. In clinical vascular laboratories, the primary method of wall shear rate estimation is the scaled ratio between the center line systolic velocity and the local arterial radius. The present study compares this method with the shear rate calculated directly from data collected using a Doppler ultrasound scanner. Blood flow in the superficial femoral artery of 20 subjects was measured during three stages of distal resistance. Analysis and display programs were written for use with the MATLAB image processing software package. The experimental values of shear rate were calculated using the formal definition and then compared to the standard estimate. In all three states of distal resistance, the experimental values were significantly higher than the estimated values by a factor of approximately 1.57. These results led to the conclusion that the direct method of measuring shear rate is more precise and should replace the estimation model in the clinical laboratory.

  6. Sphingosine induces phospholipase D and mitogen activated protein kinase in vascular smooth muscle cells.

    Science.gov (United States)

    Taher, M M; Abd-Elfattah, A S; Sholley, M M

    1998-12-01

    The enzymes phospholipase D and diacylglycerol kinase generate phosphatidic acid which is considered to be a mitogen. Here we report that sphingosine produced a significant amount of phosphatidic acid in vascular smooth muscle cells from the rat aorta. The diacylglycerol kinase inhibitor R59 949 partially depressed sphingosine induced phosphatidic acid formation, suggesting that activation of phospholipase C and diacylglycerol kinase can not account for the bulk of phosphatidic acid produced and that additional pathways such as phospholipase D may contribute to this. Further, we have shown that phosphatidylethanol was produced by sphingosine when vascular smooth muscle cells were stimulated in the presence of ethanol. Finally, as previously shown for other cell types, sphingosine stimulated mitogen-activated protein kinase in vascular smooth muscle cells.

  7. PROTECTIVE EFFECTS OF CALCIUM ANTAGONIST ON VASCULAR SYSTEM AGAINST TOXICITY INDUCED BY MERCURIC CHLORIDE

    Institute of Scientific and Technical Information of China (English)

    马欣; 厉英倩; 白宇飞; 刘明

    2004-01-01

    Objective To explore the toxic effects of mercuric chloride (HgCl2) on vascular smooth muscle as well as its relationship to calcium antagonist. Methods By using isolated vascular tension methods, we studied the effect of HgCl2 on isolated rabbit aortic rings. Results HgCl2 (1-100μmol*L-1) caused a concentration-dependent contraction of rabbit aortic rings, which did not change with phentolamin or without endothelium. In KH solution with Ca2+ , the maximum contraction amplitude reduced by(61.2±3.3)%. Nifedipine produced a concentration-dependent decrease of the maximum contraction amplitude. Conclusion Calcium antagonist has protective effects on vascular smooth muscle against damage induced by HgCl2.

  8. Influence of demographic and metabolic variables on forearm blood flow and vascular conductance in individuals without overt heart disease

    Directory of Open Access Journals (Sweden)

    Thiago E Sartori

    2010-05-01

    Full Text Available Thiago E Sartori1, Rafael AB Nunes1, Gisela T da Silva2, Sandra C da Silva1, Maria UPB Rondon1, Carlos E Negrão1, Alfredo J Mansur11Heart Institute (InCor, University of São Paulo Medical School, São Paulo, Brazil; 2Institute of Mathematics and Statistics, University of São Paulo, São Paulo, BrazilPurpose: Vascular reactivity is involved in the regulation of vascular function either in normal conditions or in the pathophysiology of cardiovascular diseases. We tested the hypothesis that vascular reactivity evaluated by forearm blood flow may vary according to demographic and metabolic variables in a cohort of individuals without any evidence of heart disease after clinical examination.Subjects and methods: We studied 186 individuals (mean age 41.4 years, standard deviation 13.1 years; 95 (51% men and 91 (49% women. We investigated forearm blood flow and vascular conductance with venous occlusion plethysmography at baseline, during handgrip isometric exercise and during the recovery phase. Demographic and laboratory data were collected. Statistical analysis was performed with mixed linear models appropriate for repeated measurements.Results: Mean forearm blood flow values in the different study conditions ranged between 1.7 ± 0.47 mL.min−1.100 mL−1 of tissue and 2.82 ± 1.13 mL.min−1.100 mL−1 of tissue. Forearm blood flow was higher in men than in women (P < 0.005 and increased as the heart rate increased during handgrip maneuver (P < 0.0001. Serum triglyceride levels were inversely related to forearm blood flow at baseline, during isometric exercise and recovery phase (P = 0.0209. Body mass index was inversely related to forearm vascular conductance at baseline, during isometric exercise and recovery phase (P = 0.0223.Conclusion: Our findings suggest that forearm blood flow and vascular conductance as a surrogate of the vascular function may be influenced by gender, heart rate, serum triglyceride levels and body mass index in

  9. UAP56 is an important mediator of Angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Sahni, Abha [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States); Wang, Nadan [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Alexis, Jeffrey, E-mail: jeffrey_alexis@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States)

    2013-02-15

    Highlights: ► Knockdown of UAP56 inhibits Angiotensin II/PDGF induced vascular smooth muscle cell proliferation. ► UAP56 is a positive regulator of E2F transcriptional activation. ► UAP56 is present in the vessel wall of low flow carotid arteries. -- Abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reported that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease.

  10. Quantification and characterization of radiation-induced changes to mandibular vascularity using micro-computed tomography.

    Science.gov (United States)

    Deshpande, Sagar Satish; Donneys, Alexis; Farberg, Aaron Samuel; Tchanque-Fossuo, Catherine N; Felice, Peter A; Buchman, Steven Richard

    2014-01-01

    Perhaps the most vexing and exigent problem confronting head and neck cancer reconstruction is overcoming the impediments of collateral damage imposed by radiation therapy (XRT) on normal surrounding tissue. Radiation therapy is detrimental to bone and soft tissue repair resulting in an unacceptably high incidence of devastating wound healing complications as well as the associated morbidity of late pathologic fractures, reduced bone healing, and osteoradionecrosis. The consequences of XRT on bone vasculature, long known to be affected by radiation, have been poorly understood. The purpose of this study was to analyze the degree by which irradiation degrades existing bone vascularity using a powerful micro-computed tomography technique to attain highly precise quantitative metrics of the vascular tree. Fourteen 400-g male Sprague-Dawley rats underwent 35 Gy of fractionated XRT at 7 Gy/d. The animals were euthanized after 28 days, and the left ventricle was fixed and injected with Microfil (MV-122; Flow Tech, Carver, Mass) contrast. Left hemimandibles were dissected and scanned using high-resolution micro-computed tomography (18-μm voxels). The vessel number, thickness, separation, connectivity, and vessel volume fraction were analyzed for the region of interest, defined to be the volume behind the third molar spanning a total distance of 5.1 mm. Stereologic analysis and subsequent analysis of variance test demonstrated a significant and quantifiable diminution in the irradiated vasculature when compared with control animals. The vessel volume fraction (0.016 vs 0.032, P ≤ 0.003) and vessel thickness (0.042 vs 0.067 mm, P ≤ 0.001) were markedly reduced. Interestingly, further analysis demonstrated no significant differences between vessel separation and vessel number. The results of our study specifically quantify the corrosive affects of XRT on the vasculature of the mandible. The data from this novel technique go even further and imply retention of blood

  11. Flow-induced corrosion behavior of absorbable magnesium-based stents.

    Science.gov (United States)

    Wang, Juan; Giridharan, Venkataraman; Shanov, Vesselin; Xu, Zhigang; Collins, Boyce; White, Leon; Jang, Yongseok; Sankar, Jagannathan; Huang, Nan; Yun, Yeoheung

    2014-12-01

    The aim of this work was to study corrosion behavior of magnesium (Mg) alloys (MgZnCa plates and AZ31 stents) under varied fluid flow conditions representative of the vascular environment. Experiments revealed that fluid hydrodynamics, fluid flow velocity and shear stress play essential roles in the corrosion behavior of absorbable magnesium-based stent devices. Flow-induced shear stress (FISS) accelerates the overall corrosion (including localized, uniform, pitting and erosion corrosions) due to the increased mass transfer and mechanical force. FISS increased the average uniform corrosion rate, the localized corrosion coverage ratios and depths and the removal rate of corrosion products inside the corrosion pits. For MgZnCa plates, an increase of FISS results in an increased pitting factor but saturates at an FISS of ∼0.15Pa. For AZ31 stents, the volume loss ratio (31%) at 0.056Pa was nearly twice that (17%) at 0Pa before and after corrosion. Flow direction has a significant impact on corrosion behavior as more severe pitting and erosion corrosion was observed on the back ends of the MgZnCa plates, and the corrosion product layer facing the flow direction peeled off from the AZ31 stent struts. This study demonstrates that flow-induced corrosion needs be understood so that Mg-based stents in vascular environments can be effectively designed.

  12. Characterization of Vortex Generator Induced Flow

    DEFF Research Database (Denmark)

    Velte, Clara Marika

    The aim of this thesis is the characterization and modeling of the longitudinal structures actuated by vortex generators. Results from generic studies performed at low Reynolds numbers have shown that the device induced vortices possess helical structure of the vortex core. Further, their ability...... to control separation and downstream evolution across the chord of a circular sector have been studied. Similar flow structures to the ones found in the generic experiments have been found in a higher Reynolds number setting, more applicable to realistic cases common to, e.g., aeronautical applications...

  13. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Kaur, Tajpreet; Goel, Rajesh Kumar; Balakumar, Pitchai

    2010-04-01

    The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor gamma agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats.

  14. Vascular endothelial growth factor (VEGF), produced by feline infectious peritonitis (FIP) virus-infected monocytes and macrophages, induces vascular permeability and effusion in cats with FIP.

    Science.gov (United States)

    Takano, Tomomi; Ohyama, Taku; Kokumoto, Aiko; Satoh, Ryoichi; Hohdatsu, Tsutomu

    2011-06-01

    Feline infectious peritonitis virus (FIPV) causes a fatal disease called FIP in Felidae. The effusion in body cavity is commonly associated with FIP. However, the exact mechanism of accumulation of effusion remains unclear. We investigated vascular endothelial growth factor (VEGF) to examine the relationship between VEGF levels and the amounts of effusion in cats with FIP. Furthermore, we examined VEGF production in FIPV-infected monocytes/macrophages, and we used feline vascular endothelial cells to examine vascular permeability induced by the culture supernatant of FIPV-infected macrophages. In cats with FIP, the production of effusion was related with increasing plasma VEGF levels. In FIPV-infected monocytes/macrophages, the production of VEGF was associated with proliferation of virus. Furthermore, the culture supernatant of FIPV-infected macrophages induced hyperpermeability of feline vascular endothelial cells. It was suggested that vascular permeability factors, including VEGF, produced by FIPV-infected monocytes/macrophages might increase the vascular permeability and the amounts of effusion in cats with FIP.

  15. 4D phase contrast flow imaging for in-stent flow visualization and assessment of stent patency in peripheral vascular stents – A phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Bunck, Alexander C., E-mail: alexander.bunck@uk-koeln.de [Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Department of Radiology, University Hospital Cologne, Kerpener Strasse 62, 50937 Cologne (Germany); Jüttner, Alena, E-mail: alenajuettner@gmx.de [Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Kröger, Jan Robert, E-mail: jr.kroeger@uni-muenster.de [Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Burg, Matthias C., E-mail: m_burg03@uni-muenster.de [Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Kugel, Harald, E-mail: kugel@uni-muenster.de [Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Niederstadt, Thomas, E-mail: tnieders@uni-muenster.de [Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Tiemann, Klaus, E-mail: Klaus.Tiemann@ukmuenster.de [Department of Cardiology and Angiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster (Germany); Schnackenburg, Bernhard, E-mail: bernhard.schnackenburg@philips.com [Philips Medical Systems DMC GmbH, Röntgenstraße 24, 22335 Hamburg (Germany); Crelier, Gerard R., E-mail: crelier@biomed.ee.ethz.ch [Institute for Biomedical Engineering, ETH and University of Zurich, ETZ F 95, Gloriastrasse 35, 8092 Zurich (Switzerland); and others

    2012-09-15

    Purpose: 4D phase contrast flow imaging is increasingly used to study the hemodynamics in various vascular territories and pathologies. The aim of this study was to assess the feasibility and validity of MRI based 4D phase contrast flow imaging for the evaluation of in-stent blood flow in 17 commonly used peripheral stents. Materials and methods: 17 different peripheral stents were implanted into a MR compatible flow phantom. In-stent visibility, maximal velocity and flow visualization were assessed and estimates of in-stent patency obtained from 4D phase contrast flow data sets were compared to a conventional 3D contrast-enhanced magnetic resonance angiography (CE-MRA) as well as 2D PC flow measurements. Results: In all but 3 of the tested stents time-resolved 3D particle traces could be visualized inside the stent lumen. Quality of 4D flow visualization and CE-MRA images depended on stent type and stent orientation relative to the magnetic field. Compared to the visible lumen area determined by 3D CE-MRA, estimates of lumen patency derived from 4D flow measurements were significantly higher and less dependent on stent type. A higher number of stents could be assessed for in-stent patency by 4D phase contrast flow imaging (n = 14) than by 2D phase contrast flow imaging (n = 10). Conclusions: 4D phase contrast flow imaging in peripheral vascular stents is feasible and appears advantageous over conventional 3D contrast-enhanced MR angiography and 2D phase contrast flow imaging. It allows for in-stent flow visualization and flow quantification with varying quality depending on stent type.

  16. Fractional flow reserve as a surrogate for inducible myocardial ischaemia.

    Science.gov (United States)

    van de Hoef, Tim P; Meuwissen, Martijn; Escaned, Javier; Davies, Justin E; Siebes, Maria; Spaan, Jos A E; Piek, Jan J

    2013-08-01

    Documentation of inducible myocardial ischaemia, related to the coronary stenosis of interest, is of increasing importance in lesion selection for percutaneous coronary intervention (PCI). Fractional flow reserve (FFR) is an easily understood, routine diagnostic modality that has become part of daily clinical practice, and is used as a surrogate technique for noninvasive assessment of myocardial ischaemia. However, the application of a single, discrete, cut-off value for FFR-guided lesion selection for PCI, and its adoption in contemporary revascularization guidelines, has limited the requirement for a thorough understanding of the physiological basis of FFR. This limitation constitutes an obstacle for the adequate use and interpretation of this technique, and also for the understanding of new and future modalities of physiological functional intracoronary testing. In this Review, we revisit the fundamental elements of coronary physiology in the absence or presence of coronary artery disease. We provide insight into three essential characteristics of FFR as a diagnostic tool in contemporary clinical practice--the theoretical framework of FFR and its associated limitations; the characteristics and role of FFR as a surrogate for noninvasively assessed myocardial ischaemia; and the requirement and associated caveats of potent vasodilatory drugs to induce maximal vasodilatation of the coronary vascular bed.

  17. Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals

    Energy Technology Data Exchange (ETDEWEB)

    Kihara, Mikihiro; Schmelzer, J.D.; Poduslo, J.F.; Curran, G.L.; Nickander, K.K.; Low, P.A. (Mayo Foundation, Rochester, MN (United States))

    1991-07-15

    Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, the authors examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG, group II received STZ plus AG, group III received STZ alone, and group IV was a control. They monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to {sup 125}I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. They suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.

  18. 18F-FDG PET imaging in detection of radiation-induced vascular disease in lymphoma survivors

    DEFF Research Database (Denmark)

    Ripa, Rasmus S.; Hag, Anne Mette; Knudsen, Andreas;

    2015-01-01

    Radiation therapy (RT) induces vascular changes that increase the risk of cardiovascular diseases in some patients. The objective was to determine if in vivo positron emission tomography (PET) with fluorodeoxyglucose (18F-FDG) can identify increased vascular inflammation in patients without changes...... in vascular intima media thickness (IMT). Patients previously receiving unilateral RT due to lymphoma were prospectively recruited (N=10). The untreated contralateral artery functioned as control. All patients underwent a dedicated vascular PET/CT. Vascular tracer uptake was quantified by drawing regions...... (P=0.04). Measurement of IMT showed that 4 patients had the highest thickness in the irradiated side, while the other 4 patients had the highest thickness in the non-irradiated side (P=0.8). In conclusion, we found that (18)F-FDG PET imaging may be used to detect vascular changes induced by RT...

  19. Blood flow interplays with elastin: collagen and MMP: TIMP ratios to maintain healthy vascular structure and function

    Directory of Open Access Journals (Sweden)

    Poulami Basu

    2010-03-01

    Full Text Available Poulami Basu, Utpal Sen, Neetu Tyagi, Suresh C TyagiDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USAAbstract: Differential vascular remodeling is one of the major mechanisms of heterogeneity in atherosclerosis. The structural and functional heterogeneity between arteries and veins determines the degree of vascular remodeling. Matrix metalloproteases (MMPs and their tissue inhibitors (TIMPs play key roles in vascular structural and functional remodeling. We hypothesized that the level of blood flow in different arteries and veins caused structural and functional heterogeneity that ultimately determined potential vascular remodeling. To test this hypothesis, in vivo blood flow and blood pressure in the aorta, carotid, femoral artery, and femoral vein was measured in male Sprague-Dawley rats (weight 380–400 gm. Arterial and venous pressures were measured by PE-50 catheter cannulation. Blood flow was measured by a transonic ultrasound system. The aortic arch, femoral and carotid arteries, and abdominal vena cava were isolated to determine the expression of MMP-2, -9, -12, and -13 and TIMP-1, -3, and -4 by Western blot and in gelatin gel zymography. Masson trichrome and van Gieson stains were used to stain the histologic tissue sections. The results revealed that blood flow was higher in the aorta and carotid artery than the femoral artery and vein. MMP-9 and MMP-13 were higher in the carotid artery in comparison with the other blood vessels, while TIMP-3 showed higher expression in the aorta than the arteries. Further, the MMP-9 activity was significantly higher in the carotid artery than in the aorta and femoral artery. There was a higher degree of basement membrane collagen in the femoral artery and therefore a low elastin: collagen ratio, while in the carotid artery a higher level of elastin and, therefore, a high elastin: collagen ratio was found. The results suggested that medial

  20. Downregulation of P16 promotes cigarette smoke extract-induced vascular smooth muscle cell proliferation via preventing G1/S phase transition.

    Science.gov (United States)

    Guo, Tao; Chai, Xiangping; Liu, Qiming; Peng, Wen; Peng, Zhenyu; Cai, Yuzhong

    2017-07-01

    The proliferation of vascular smooth muscle cells (VSMCs) serves an important role in cigarette smoking-associated vascular diseases; however, the underlying mechanisms responsible for this remain unclear. The aim of the present study was to elucidate the role of P16 in cigarette smoke extract (CSE)-induced VSMC proliferation and the underlying mechanism responsible. Human aortic smooth muscle cells (HAOSMCs) were exposed to CSE, and an MTT assay and flow cytometry were performed to evaluate cell proliferation and cell cycle distribution. Western blotting was conducted to examine protein expression and bisulfite genomic sequencing polymerase chain reaction was used to determine the methylation status of the P16 promoter CpG island. It was demonstrated that treatment with CSE significantly promoted the proliferation of HAOSMCs in a concentration- and time-dependent manner and induced a downregulation in P16 expression (all PP16 promoter, which led to a significant decrease in its transcriptional activity and significantly reduced P16 protein expression in HAOSMCs (both PP16 downregulation induced a significant increase in the expression of cyclin-dependent kinase (CDK) 4, CDK6 and phosphorylated retinoblastoma (p-Rb) protein (all PP16 inhibited CSE-induced cell proliferation through inducing cell cycle arrest in G1 phase (PP16 may be associated with the CSE-induced proliferation of VSMCs, suggesting that P16 serves a role in the development of cigarette smoke-associated vascular diseases.

  1. Knockdown of connexin 43 attenuates balloon injury-induced vascular restenosis through the inhibition of the proliferation and migration of vascular smooth muscle cells.

    Science.gov (United States)

    Han, Xiao-Jian; He, Dan; Xu, Liang-Jing; Chen, Min; Wang, Yi-Qi; Feng, Jiu-Geng; Wei, Min-Jun; Hong, Tao; Jiang, Li-Ping

    2015-11-01

    Coronary artery disease (CAD) or atherosclerotic heart disease is one of the most common types of cardiovascular disease. Although percutaneous coronary intervention [PCI or percutaneous transluminal coronary angioplasty (PTCA)] is a mature, well-established technique used to treat atherosclerotic heart disease, its long‑term therapeutic effects are compromised by a high incidence of vascular restenosis (RS) following angioplasty. In our previous study, we found that the principal gap junction protein, connexin 43 (Cx43), in vascular smooth muscle cells (VSMCs) was involved in the development of vascular RS following angioplasty-induced balloon injury. However, the exact role action of Cx43 in vascular RS remains unclear. In the present study, we aimed to further examine whether the knockdown of Cx43 attenuates the development of vascular RS through the inhibition of the proliferation and migration of VSMCs. We found that the use of a lentiviral vector expressing shRNA targeting Cx43 (Cx43‑RNAi-LV) efficiently silenced the mRNA and protein expression of Cx43 in cultured VSMCs. In addition, MTT and Transwell assays were used to examined the proliferation and migration of the VSMCs, respectively. The results revealed that the knockdown of Cx43 by Cx43-RNAi-LV at a multiplicity of infection (MOI) of 100 significantly inhibited the proliferation and migration of the VSMCs in vitro. Notably, the knockdown of Cx43 also effectively attenuated the development of vascular RS and intimal hyperplasia following balloon injury in vivo. Taken together, our data suggest that Cx43 is involved in the development of vascular RS and intimal hyperplasia through the regulation of the proliferation and migration of VSMCs. Thus, the present study provides new insight into the pathogenesis of vascular RS, and suggests that further comfirms that Cx43 may well be a novel potential pharmacological target for preventing vascular RS following PCI.

  2. A novel mechanism of diabetic vascular endothelial dysfunction: Hypoadiponectinemia-induced NLRP3 inflammasome activation.

    Science.gov (United States)

    Zhang, Jinglong; Xia, Linying; Zhang, Fen; Zhu, Di; Xin, Chao; Wang, Helin; Zhang, Fuyang; Guo, Xian; Lee, Yan; Zhang, Ling; Wang, Shan; Guo, Xiong; Huang, Chong; Gao, Feng; Liu, Yi; Tao, Ling

    2017-02-12

    It has been well documented that hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. However, the exact molecular mechanism which mediates this process has not been fully described. The current study aimed to investigate the role of hypoadiponectinemia-induced NLRP3 inflammasome activation in diabetic vascular endothelial dysfunction and its molecular mechanism. Male adult adiponectin knockout mice and wild type mice were fed with a high fat diet to establish a type 2 diabetic mellitus model. In addition, human umbilical vein endothelial cells (HUVECs) were cultured and subjected to high glucose/high fat (HG/HF). The NLRP3 inflammasome activation was increased in type 2 diabetic mice and treatment of diabetic aortic segments with MCC950, a potent selective inhibitor of NLRP3 inflammasome ex vivo improved endothelial-dependent vasorelaxation. NLRP3 inflammasome activation and vascular endothelial injury were significantly increased in APN-KO mice compared with WT mice in diabetes and MCC950 decreased diabetic vascular endothelial dysfunction to comparable levels in APN-KO mice and WT mice. Adiponectin could decrease NLRP3 inflammasome activation and attenuate endothelial cell injury, which was abolished by NLRP3 inflammasome overexpression. Inhibition of peroxynitrite formation preferentially attenuated NLRP3 inflammasome activation in APN-KO diabetic mice. The current study demonstrated for the first time that hypoadiponectinemia-induced NLRP3 inflammasome activation was a novel mechanism of diabetic vascular endothelial dysfunction.

  3. SIRT1 inhibits angiotensin Ⅱ-induced vascular smooth muscle cell hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Li Li; Chihchuan Liang; Peng Gao; Huina Zhang; Houzao Chen; Wei Zheng; Xiang Lv; Tingting Xu; Yusheng Wei; Depei Liu

    2011-01-01

    Angiotensin Ⅱ (Ang Ⅱ) stimulates vascular smooth muscle cell (VSMC) hypertrophy as a critical event in the development of vascular diseases such as atherosclerosis.Sirtuin (SIRT) 1, a nicotinamide adenine dinucleotide dependent deacetylase, has been demonstrated to exert protective effects in atherosclerosis by promoting endo-thelium-dependent vascular relaxation and reducing macrophage foam cell formation, but its role in VSMC hypertrophy remains unknown. In this study, we tried to investigate the effect of SIRTI on Ang Ⅱ-induced VSMC hypertrophy. Results showed that adenoviral-mediated over-expression of SIRT1 significantly inhibited Ang Ⅱ-induced VSMC hypertrophy, while knockdown of SIRT1 by RNAi resulted in an increased [3H]-leucine incorpor-ation of VSMC. Accordingly, nicotinamide adenine dinu-cleotide phosphate oxidase 1 (Nox1) expression induced by Ang Ⅱ was inhibited by SIRT1 in VSMCs. SIRT1 acti-vator resveratrol decreased, whereas endogenous SIRT1 inhibitor nicotinamide increased Nox1 expression in A7r5 VSMCs. Furthermore, transcription factor GATA-6 was involved in the down-regulation of Nox1 expression by SIRT1. These results provide new insight into SIRTI's anti-atherogenic properties by suppressing Ang Ⅱ-induced VSMC hypertrophy.

  4. The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

    2010-10-01

    The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

  5. Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-{kappa}B signaling

    Energy Technology Data Exchange (ETDEWEB)

    Tsou, Tsui-Chun, E-mail: tctsou@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Yeh, Szu-Ching; Tsai, Feng-Yuan; Lin, Ho-Jane [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Cheng, Tsun-Jen [Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan (China); Chao, How-Ran [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan (China); Tai, Lin-Ai [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)

    2010-11-15

    This study investigated inflammatory effects of zinc oxide (ZnO) particles on vascular endothelial cells. The effects of 50 and 100-nm ZnO particles on human umbilical vein endothelial cells (HUVECs) were characterized by assaying cytotoxicity, cell proliferation, and glutathione levels. A marked drop in survival rate was observed when ZnO concentration was increased to 45 {mu}g/ml. ZnO concentrations of {<=}3 {mu}g/ml resulted in increased cell proliferation, while those of {<=}45 {mu}g/ml caused dose-dependent increases in oxidized glutathione levels. Treatments with ZnO concentrations {<=}45 {mu}g/ml were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) protein, an indicator of vascular endothelium inflammation, revealing that ZnO particles induced a dose-dependent increase in ICAM-1 expression and marked increases in NF-{kappa}B reporter activity. Overexpression of I{kappa}B{alpha} completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-{kappa}B plays a pivotal role in regulation of ZnO-induced inflammation in HUVECs. Additionally, TNF-{alpha}, a typical inflammatory cytokine, induced ICAM-1 expression in an NF-{kappa}B-dependent manner, and ZnO synergistically enhanced TNF-{alpha}-induced ICAM-1 expression. Both 50 and 100-nm ZnO particles agglomerated to similar size distributions. This study reveals an important role for ZnO in modulating inflammatory responses of vascular endothelial cells via NF-{kappa}B signaling, which could have important implications for treatments of vascular disease.

  6. Vascular flow reserve as a link between long-term blood pressure level and physical performance capacity in mammals

    DEFF Research Database (Denmark)

    Poulsen, Christian B; Damkjær, Mads; Hald, Bjørn O

    2016-01-01

    function producing a high precapillary resistance and thus a high vascular flow reserve is associated with an increase in network inlet pressure. Assuming that network properties are independent of body mass, and that inlet pressure of the microvascular network is a proxy for arterial pressure, the study......Mean arterial pressure (MAP) is surprisingly similar across different species of mammals, and it is, in general, not known which factors determine the arterial pressure level. Mammals often have a pronounced capacity for sustained physical performance. This capacity depends on the vasculature...... having a flow reserve that comes into play as tissue metabolism increases. We hypothesize that microvascular properties allowing for a large vascular flow reserve is linked to the level of the arterial pressure.To study the interaction between network properties and network inlet pressure, we developed...

  7. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  8. TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries

    Institute of Scientific and Technical Information of China (English)

    Cui-ling LIU; Yu HUANG; Ching-yuen NGAI; Yuk-ki LEUNG; Xiao-qiang YAO

    2006-01-01

    Aim: To test the possible involvement of TRPC3 in agonist-induced relaxation and flow-induced vasodilation in rat small mesenteric arteries. Methods: Male Sprague-Dawley rats were used in the present study. After 72 h-treatment of antisense oligo via tail vein injection, isometric tension and isobaric diameter measurement were carried out with isolated mesenteric artery segments by using either a Pressure Myograph or a Multi Myograph system. Endothelial [Ca2+]i changes were measured with a MetaFluor imaging system in response to flow or to 30 nmol/L bradykinin. Results: Immunohistochemical study showed that the 72 h-treatment of antisense oligo via tail vein injection markedly decreased the TRPC3 expression in mesenteric arteries, indicating the effectiveness of the antisense oligo. Isometric tension and isobaric diameter measurement showed that, although the antisense oligo treatment did not affect histamine-, ATP-, and CPA-induced relaxation, it did reduce the magnitude of flow-induced vasodilation by approximately 13% and decreased bradykinin-induced vascular relaxation with its EC50 value raised by nearly 3-fold. Endothelial [Ca2+]i measurement revealed that treatment of the arteries with antisense oligos significantly attenuated the magnitude of endothelial [Ca2+]i rise in response to flow and to 30 nmol/L bradykinin. Conclusion: The results suggest that TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries probably by mediating the Ca2+ influx into endothelial cells.

  9. Vascular coupling induces synchronization, quasiperiodicity, and chaos in a nephron tree

    DEFF Research Database (Denmark)

    Marsh, D. J.; Sosnovtseva, Olga; Mosekilde, Erik;

    2007-01-01

    The paper presents a study of synchronization phenomena in a system of 22 nephrons supplied with blood from a common cortical radial artery. The nephrons are assumed to interact via hemodynamic and vascularly propagated coupling, both mediated by vascular connections. Using anatomic and physiolog......The paper presents a study of synchronization phenomena in a system of 22 nephrons supplied with blood from a common cortical radial artery. The nephrons are assumed to interact via hemodynamic and vascularly propagated coupling, both mediated by vascular connections. Using anatomic...... and physiological criteria, the nephrons are divided into groups: cortical nephrons and medullary nephrons with short, intermediate and long Henle loops. Within each of these groups the delay parameters of the internal feedback regulation are given a random component to represent the internephron variability....... For parameters that generate simple limit cycle dynamics in the pressure and flow regulation of single nephrons, the ensemble of coupled nephrons showed steady state, quasiperiodic or chaotic dynamics, depending on the interaction strengths and the arterial blood pressure. When the solutions were either...

  10. Puerarin decreases hypoxia inducible factor-1 alpha in the hippocampus of vascular dementia rats

    Institute of Scientific and Technical Information of China (English)

    Haiqin Wu; Huqing Wang; Bei Zhang; Guilian Zhang; Ru Zhang; Lingfeng Zhang

    2012-01-01

    In this study, a rat vascular dementia model was established by permanent bilateral common carotid arterial occlusion. Rats were intraperitoneally injected with puerarin 3 days before modeling, for 45 successive days. Results demonstrated that in treated animals hippocampal structures were clear, nerve cells arranged neatly, and cytoplasm was rich in Nissl bodies. The number of cells positive for hypoxia inducible factor-1 alpha, erythropoietin and endothelial nitric oxide synthase was reduced; and the learning and memory abilities of rats were significantly improved. Our experimental findings indicate that puerarin can significantly improve learning and memory in a vascular dementia model, and that the underlying mechanism may be associated with the regulation of the expression of hypoxia inducible factor-1 alpha.

  11. Docosahexaenoic Acid Supplemented Diet Influences the Orchidectomy-Induced Vascular Dysfunction in Rat Mesenteric Arteries

    Science.gov (United States)

    Villalpando, Diva M.; Navarro, Rocío; del Campo, Lara; Largo, Carlota; Muñoz, David; Tabernero, María; Baeza, Ramiro; Otero, Cristina; García, Hugo S.; Ferrer, Mercedes

    2017-01-01

    Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy. PMID:28068359

  12. Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects.

    Science.gov (United States)

    Sakurada, Takumi; Ishizawa, Keisuke; Imanishi, Masaki; Izawa-Ishizawa, Yuki; Fujii, Shoko; Tominaga, Erika; Tsuneishi, Teppei; Horinouchi, Yuya; Kihira, Yoshitaka; Ikeda, Yasumasa; Tomita, Shuhei; Aihara, Ken-ichi; Minakuchi, Kazuo; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2013-01-01

    Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress.

  13. Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth

    Energy Technology Data Exchange (ETDEWEB)

    Ashino, T.; Varadarajan, S.; Urao, N.; Oshikawa, J.; Chen, G. -F.; Wang, H.; Huo, Y.; Finney, L.; Vogt, S.; McKinney, R. D.; Maryon, E. B.; Kaplan, J. H.; Ushio-Fukai, M.; Fukai, T. (Biosciences Division); ( XSD); ( PSC-USR); (Univ. of Illinois at Chicago); (Univ. of Minnesota)

    2010-09-09

    Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model. These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.

  14. AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young; Woo, Chang-Hoon [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Kang, Young Jin; Lee, Kwang Youn [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-09-16

    Highlights: {yields} An aging model was established by stimulating VSMC with adriamycin. {yields} Adriamycin increased p-LKB1, p-AMPK, p53 and p21 expressions. {yields} Inhibition of AMPK diminished SA-{beta}-gal staining and restored VSMC proliferation. {yields} p53 and p21 siRNA attenuated adriamycin-induced SA-{beta}-gal staining in VSMC. {yields} p53-p21 pathway is a mediator of LKB1/AMPK induced VSMC senescence. -- Abstract: Vascular cells have a limited lifespan with limited cell proliferation and undergo cellular senescence. The functional changes associated with cellular senescence are thought to contribute to age-related vascular disorders. AMP-activated protein kinase (AMPK) has been discussed in terms of beneficial or harmful effects for aging-related diseases. However, the detailed functional mechanisms of AMPK are largely unclear. An aging model was established by stimulating vascular smooth muscle cell (VSMC) with adriamycin. Adriamycin progressively increased the mRNA and protein expressions of AMPK. The phosphorylation levels of LKB1 and acetyl-CoA carboxylase (ACC), the upstream and downstream of AMPK, were dramatically increased by adriamycin stimulation. The expressions of p53 and p21, which contribute to vascular senescence, were also increased. Inhibition of AMPK diminished senescence-associated {beta}-galactosidase (SA-{beta}-gal) staining, and restored VSMC proliferation. Cytosolic translocation of LKB1 by adriamycin could be a mechanism for AMPK activation in senescence. Furthermore, p53 siRNA and p21 siRNA transfection attenuated adriamycin-induced SA-{beta}-gal staining. These results suggest that LKB1 dependent AMPK activation elicits VSMC senescence and p53-p21 pathway is a mediator of LKB1/AMPK-induced senescence.

  15. Inhibitive effects of anti-oxidative vitamins on mannitol-induced apoptosis of vascular endothelial cells

    OpenAIRE

    Pan, Kai-yu; Shen, Mei-ping; Ye, Zhi-Hong; Dai, Xiao-na; Shang, Shi-qiang

    2006-01-01

    Objective: Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Methods: Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was performed with normal saline (group B), vitamin C (group C) and vitamin E (group D). Blood vessel injury was assessed under electron...

  16. Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds.

    Science.gov (United States)

    Wang, Jianglin; Yang, Mingying; Zhu, Ye; Wang, Lin; Tomsia, Antoni P; Mao, Chuanbin

    2014-08-01

    A virus-activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high-density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs.

  17. An inguinal mass with local vascular lesions induced by a lymphatic filaria.

    Science.gov (United States)

    Abdel-Hameed, Ahmed A; Dura, Wieslaw T; Alkhalife, Ibrahim S

    2004-08-01

    A 47-year-old Indian male presented with an inguinal mass clinically suspicious as a tumor. Histological examination of the excised mass demonstrated tissue reaction to degenerating intravascular adult filarial worms. The worms have been identified as a lymphatic filariae, most probably Wuchereria bancrofti. The case report underscores the need to maintain suspicion of genitourinary filarial lesions in non-endemic areas and describes atypical vascular lesions induced by lymphatic filariae.

  18. Flow Induced Electrification of Liquid Insulated Systems.

    Science.gov (United States)

    Washabaugh, Andrew Patrick

    1995-01-01

    The transport or motion of semi-insulating liquids has led to flow induced static electrification and catastrophic failures in several industries. While techniques for reducing the hazard have been developed, the roles of seemingly important parameters are poorly understood. The objective of this thesis was to measure and understand the fundamental parameters of the flow electrification process that, together with the laws of electroquasistatics and physicochemical hydrodynamics, can be used to predict the performance of complex flow systems, with particular attention to transformer applications. A rotating cylindrical electrode apparatus, which provided cylindrical Couette flow, was used to simulate flow electrification in an electric power transformer. The apparatus had Shell Diala A transformer oil filling the annulus between coaxial cylindrical stainless steel electrodes that were either bare metal, or covered by a thin copper sheet and/or EHV-Weidmann HiVal pressboard insulation. Extensive experiments characterized the time transient and steady state behavior of the electrification through measurements of the volume charge density, the terminal voltage, and the terminal current as the system was driven out of equilibrium by changes in the flow rate (inner cylinder rotation rates of 100-1400 rpm, Reynolds numbers of 5 times 10^3-5 times 10^5), temperature (15-70 ^circ), insulation moisture content (0.5-20 ppm in the oil), applied voltage (0-2 kV DC), and concentration of the non-ionizable anti-static additive 1,2,3 benzotriazole (BTA, 0-60 ppm). Generally, the electrification increased with flow rate and temperature but the BTA appeared to cause competing effects: it decreased the volume charge density on the liquid side of the interface (by a factor of 4), which reduces the electrification, but also decreased the oil conductivity (by a factor of 10), which enhances the electrification. A critical oil BTA concentration of 5 -8 ppm minimized the electrification

  19. 4D magnetic resonance flow imaging for estimating pulmonary vascular resistance in pulmonary hypertension.

    Science.gov (United States)

    Kheyfets, Vitaly O; Schafer, Michal; Podgorski, Chris A; Schroeder, Joyce D; Browning, James; Hertzberg, Jean; Buckner, J Kern; Hunter, Kendal S; Shandas, Robin; Fenster, Brett E

    2016-10-01

    To develop an estimate of pulmonary vascular resistance (PVR) using blood flow measurements from 3D velocity-encoded phase contract magnetic resonance imaging (here termed 4D MRI). In all, 17 patients with pulmonary hypertension (PH) and five controls underwent right heart catheterization (RHC), 4D and 2D Cine MRI (1.5T) within 24 hours. MRI was used to compute maximum spatial peak systolic vorticity in the main pulmonary artery (MPA) and right pulmonary artery (RPA), cardiac output, and relative area change in the MPA. These parameters were combined in a four-parameter multivariate linear regression model to arrive at an estimate of PVR. Agreement between model predicted and measured PVR was also evaluated using Bland-Altman plots. Finally, model accuracy was tested by randomly withholding a patient from regression analysis and using them to validate the multivariate equation. A decrease in vorticity in the MPA and RPA were correlated with an increase in PVR (MPA: R(2) = 0.54, P < 0.05; RPA: R(2) = 0.75, P < 0.05). Expanding on this finding, we identified a multivariate regression equation that accurately estimates PVR (R(2) = 0.94, P < 0.05) across severe PH and normotensive populations. Bland-Altman plots showed 95% of the differences between predicted and measured PVR to lie within 1.49 Wood units. Model accuracy testing revealed a prediction error of ∼20%. A multivariate model that includes MPA relative area change and flow characteristics, measured using 4D and 2D Cine MRI, offers a promising technique for noninvasively estimating PVR in PH patients. J. MAGN. RESON. IMAGING 2016;44:914-922. © 2016 International Society for Magnetic Resonance in Medicine.

  20. Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Penghao [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Xie, Qihai [Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai (China); Wei, Tong [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Yichen [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Hong, E-mail: hchen100@shsmu.edu.cn [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Shen, Weili, E-mail: wlshen@sibs.ac.cn [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2015-12-04

    Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

  1. Optical oximetry of volume-oscillating vascular compartments: contributions from oscillatory blood flow

    Science.gov (United States)

    Kainerstorfer, Jana M.; Sassaroli, Angelo; Fantini, Sergio

    2016-10-01

    We present a quantitative analysis of dynamic diffuse optical measurements to obtain oxygen saturation of hemoglobin in volume oscillating compartments. We used a phasor representation of oscillatory hemodynamics at the heart rate and respiration frequency to separate the oscillations of tissue concentrations of oxyhemoglobin (O) and deoxyhemoglobin (D) into components due to blood volume (subscript V) and blood flow (subscript F): O=OV+OF, D=DV+DF. This is achieved by setting the phase angle Arg(OF)-Arg(O), which can be estimated by a hemodynamic model that we recently developed. We found this angle to be -72 deg for the cardiac pulsation at 1 Hz, and -7 deg for paced breathing at 0.1 Hz. Setting this angle, we can obtain the oxygen saturation of hemoglobin of the volume-oscillating vascular compartment, SV=|OV|/(|OV|+|DV|). We demonstrate this approach with cerebral near-infrared spectroscopy measurements on healthy volunteers at rest (n=4) and during 0.1 Hz paced breathing (n=3) with a 24-channel system. Rest data at the cardiac frequency were used to calculate the arterial saturation, S(a); over all subjects and channels, we found ==0.96±0.02. In the case of paced breathing, we found =0.66±0.14, which reflects venous-dominated hemodynamics at the respiratory frequency.

  2. Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache.

    Science.gov (United States)

    Gottselig, R; Messlinger, K

    2004-03-01

    Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.

  3. Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet

    Science.gov (United States)

    Carillon, Julie; Jover, Bernard; Cristol, Jean-Paul; Rouanet, Jean-Max; Richard, Sylvain; Virsolvy, Anne

    2016-01-01

    Background Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD), have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity. Objective We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity. Design and results The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L.) Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD. Conclusions Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome–induced cardiovascular trouble. PMID:27834185

  4. Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet.

    Science.gov (United States)

    Carillon, Julie; Jover, Bernard; Cristol, Jean-Paul; Rouanet, Jean-Max; Richard, Sylvain; Virsolvy, Anne

    2016-01-01

    Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD), have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity. We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity. The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L.) Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD. Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome-induced cardiovascular trouble.

  5. Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet

    Directory of Open Access Journals (Sweden)

    Julie Carillon

    2016-11-01

    Full Text Available Background: Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD, have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity. Objective: We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity. Design and results: The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L. Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD. Conclusions: Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome–induced cardiovascular trouble.

  6. Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification.

    Science.gov (United States)

    Paloian, Neil J; Leaf, Elizabeth M; Giachelli, Cecilia M

    2016-05-01

    Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease. The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of procalcific and anticalcific factors. In the chronic kidney disease population, an elevated phosphate burden is both highly prevalent and a known risk factor for ectopic calcification. Here we tested whether osteopontin, an inhibitor of calcification, protects against high phosphate load-induced nephrocalcinosis and vascular calcification. Osteopontin knockout mice were placed on a high phosphate diet for 11 weeks. Osteopontin deficiency together with phosphate overload caused uremia, nephrocalcinosis characterized by substantial renal tubular and interstitial calcium deposition, and marked vascular calcification when compared with control mice. Although the osteopontin-deficient mice did not exhibit hypercalcemia or hyperphosphatemia, they did show abnormalities in the mineral metabolism hormone fibroblast growth factor-23. Thus, endogenous osteopontin plays a critical role in the prevention of phosphate-induced nephrocalcinosis and vascular calcification in response to high phosphate load. A better understanding of osteopontin's role in phosphate-induced calcification will hopefully lead to better biomarkers and therapies for this disease, especially in patients with chronic kidney disease and other at-risk populations.

  7. The effects of vasoactive agents on flow through saphenous vein grafts during lower-extremity peripheral vascular surgery.

    Science.gov (United States)

    Maslow, Andrew D; Bert, Arthur; Slaiby, Jeffrey; Carney, William; Marcaccio, Edward

    2007-06-01

    The purpose of this study was to assess the effects of hemodynamic alterations on vein graft flow during peripheral vascular surgery. It was hypothesized that vasopressors can be administered without compromising flow through the vein grafts. Tertiary care center, university medical center. Randomized placebo-controlled double-blinded study. The effects of phenylephrine, epinephrine, milrinone, intravenous fluid, and placebo on newly constructed peripheral vein grafts were assessed in 60 patients (12 patients in each of 5 groups). Systemic and central hemodynamics were measured by using intra-arterial and pulmonary artery catheters. Vein graft flow was measured by using a transultrasonic flow probe (Transultrasonic Inc, Ithaca, NY). Phenylephrine increased systemic mean blood pressure (mBP) (68.2-94.0 mmHg, p < 0.01), systemic vascular resistance (SVR) (1,091-1,696 dynes x sec x cm(-5), p < 0.001), and vein graft flow (39.5-58.9 mL/min, p < 0.01), whereas cardiac output remained unchanged. Epinephrine resulted in increased cardiac output (4.4-6.9 L/min, p < 0.01) and mBP (72.7-89.1 mmHg, p < 0.01), whereas vein graft flow was reduced in 6 of 12 patients. Intravenous fluid administration resulted in a relatively smaller increase in graft flow (37.6-46.0 mL/min, p < 0.05), an increase in cardiac output, and an insignificant decrease in SVR. Other treatments had either little or no effect on vein graft flow. The study hypothesis was partly supported. Although both phenylephrine and epinephrine increased blood pressure, only the former increased vein graft flow in all patients. In conjunction with increases in graft flow after fluid administration, these data suggest that factors affecting vein graft flow are not just simply related to systemic hemodynamics.

  8. Endothelin-1 mediates intermittent hypoxia-induced inflammatory vascular remodeling through HIF-1 activation.

    Science.gov (United States)

    Gras, Emmanuelle; Belaidi, Elise; Briançon-Marjollet, Anne; Pépin, Jean-Louis; Arnaud, Claire; Godin-Ribuot, Diane

    2016-02-15

    Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality, and apnea-induced intermittent hypoxia (IH) is known to promote various cardiovascular alterations such as vascular remodeling. However, the mechanisms that underlie IH remain incompletely investigated. We previously demonstrated that the hypoxia-inducible factor-1 (HIF-1) and endothelin-1 (ET-1) are involved in arterial hypertension and myocardial susceptibility to infarction induced by IH. Thus the objective of the present study was to investigate whether both ET-1 and HIF-1 were also involved in the vascular inflammatory remodeling induced by IH. Mice partially deficient for the Hif1α gene (HIF-1α(+/-)) and their wild-type equivalents, as well as C57BL/6J mice, treated or not with bosentan, a dual endothelin receptor antagonist, were exposed to IH or normoxia for 2 wk, 8 h/day. Splenocyte proliferative and secretory capacities, aortic nuclear factor-κB (NF-κB) and HIF-1 activities, and expression of cytokines and intima-media thickness (IMT) were measured. IH induced a systemic and aortic inflammation characterized by an increase in splenocyte proliferative and secretory capacities, aortic NF-κB activity, and cytokine expression in the aortic wall. This was accompanied by an increase in IMT. These modifications were prevented in HIF-1α(+/-) and bosentan-treated mice. The results of this study suggest that ET-1 is a major contributor to the vascular inflammatory remodeling induced by OSA-related IH, probably through HIF-1-dependent activation of NF-κB.

  9. Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression

    Directory of Open Access Journals (Sweden)

    Currie Margaret J

    2006-12-01

    Full Text Available Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia. Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1, controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A, was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.

  10. Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells.

    Science.gov (United States)

    Guo, Ning; Chen, Fangyuan; Zhou, Juan; Fang, Yuan; Li, Hongbing; Luo, Yongbai; Zhang, Yong

    2015-10-01

    Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents, not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the reendothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next generation of DES. In this study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells in both dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in rat aortic endothelial cells in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS), which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through upregulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced reendothelialization delay.

  11. ALDOSTERONE-INDUCED VASCULAR REMODELING AND ENDOTHELIAL DYSFUNCTION REQUIRE FUNCTIONAL ANGIOTENSIN TYPE 1a RECEPTORS

    OpenAIRE

    Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C.; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M.; Paradis, Pierre; Ernesto L Schiffrin

    2016-01-01

    We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors (MR) in Agtr1a−/− and wild-type mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure by ~30 mmHg in wild-type mice, and ~50 mmHg in Agtr1a−/− mice. Aldosterone induced aortic and small artery remodeling and impaired endothelium-dependent relaxation in wild-type mice, ...

  12. Nitroglycerin induces DNA damage and vascular cell death in the setting of nitrate tolerance.

    Science.gov (United States)

    Mikhed, Yuliya; Fahrer, Jörg; Oelze, Matthias; Kröller-Schön, Swenja; Steven, Sebastian; Welschof, Philipp; Zinßius, Elena; Stamm, Paul; Kashani, Fatemeh; Roohani, Siyer; Kress, Joana Melanie; Ullmann, Elisabeth; Tran, Lan P; Schulz, Eberhard; Epe, Bernd; Kaina, Bernd; Münzel, Thomas; Daiber, Andreas

    2016-07-01

    Nitroglycerin (GTN) and other organic nitrates are widely used vasodilators. Their side effects are development of nitrate tolerance and endothelial dysfunction. Given the potential of GTN to induce nitro-oxidative stress, we investigated the interaction between nitro-oxidative DNA damage and vascular dysfunction in experimental nitrate tolerance. Cultured endothelial hybridoma cells (EA.hy 926) and Wistar rats were treated with GTN (ex vivo: 10-1000 µM; in vivo: 10, 20 and 50 mg/kg/day for 3 days, s.c.). The level of DNA strand breaks, 8-oxoguanine and O (6)-methylguanine DNA adducts was determined by Comet assay, dot blot and immunohistochemistry. Vascular function was determined by isometric tension recording. DNA adducts and strand breaks were induced by GTN in cells in vitro in a concentration-dependent manner. GTN in vivo administration leads to endothelial dysfunction, nitrate tolerance, aortic and cardiac oxidative stress, formation of DNA adducts, stabilization of p53 and apoptotic death of vascular cells in a dose-dependent fashion. Mice lacking O (6)-methylguanine-DNA methyltransferase displayed more vascular O (6)-methylguanine adducts and oxidative stress under GTN therapy than wild-type mice. Although we were not able to prove a causal role of DNA damage in the etiology of nitrate tolerance, the finding of GTN-induced DNA damage such as the mutagenic and toxic adduct O (6)-methylguanine, and cell death supports the notion that GTN based therapy may provoke adverse side effects, including endothelial function. Further studies are warranted to clarify whether GTN pro-apoptotic effects are related to an impaired recovery of patients upon myocardial infarction.

  13. Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress.

    Science.gov (United States)

    Haberzettl, Petra; O'Toole, Timothy E; Bhatnagar, Aruni; Conklin, Daniel J

    2016-12-01

    Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress. Mice fed control (10-13% kcal fat) and high-fat (60% kcal fat, HFD) diets, treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) or mice overexpressing lung-specific extracellular superoxide dismutase (ecSOD) were exposed to HEPA-filtered air or to concentrated PM2.5 (CAP) for 9 or 30 days, and changes in systemic and organ-specific insulin sensitivity and inflammation were measured. In control diet-fed mice, exposure to CAP for 30 days decreased insulin-stimulated Akt phosphorylation in lung, heart, and aorta but not in skeletal muscle, adipose tissue, and liver and did not affect adiposity or systemic glucose tolerance. In HFD-fed mice, 30-day CAP exposure suppressed insulin-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation in skeletal muscle and increased adipose tissue inflammation and systemic glucose intolerance. In control diet-fed mice, a 9-day CAP exposure was sufficient to suppress insulin-stimulated Akt and eNOS phosphorylation and to decrease IκBα (inhibitor of the transcription factor NF-κB levels in the aorta. Treatment with the antioxidant TEMPOL or lung-specific overexpression of ecSOD prevented CAP-induced vascular insulin resistance and inflammation. Short-term exposure to PM2.5 induces vascular insulin resistance and inflammation triggered by a mechanism involving pulmonary oxidative stress. Suppression of vascular insulin signaling by PM2.5 may accelerate the progression to systemic insulin resistance, particularly in the context of diet-induced obesity. Citation: Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. 2016. Exposure to fine

  14. Wall-Less Flow Phantoms With Tortuous Vascular Geometries: Design Principles and a Patient-Specific Model Fabrication Example.

    Science.gov (United States)

    Ho, Chung Kit; Chee, Adrian J Y; Yiu, Billy Y S; Tsang, Anderson C O; Chow, Kwok Wing; Yu, Alfred C H

    2017-01-01

    Flow phantoms with anatomically realistic geometry and high acoustic compatibility are valuable investigative tools in vascular ultrasound studies. Here, we present a new framework to fabricate ultrasound-compatible flow phantoms to replicate human vasculature that is tortuous, nonplanar, and branching in nature. This framework is based upon the integration of rapid prototyping and investment casting principles. A pedagogical walkthrough of our engineering protocol is presented in this paper using a patient-specific cerebral aneurysm model as an exemplar demonstration. The procedure for constructing the flow circuit component of the phantoms is also presented, including the design of a programmable flow pump system, the fabrication of blood mimicking fluid, and flow rate calibration. Using polyvinyl alcohol cryogel as the tissue mimicking material, phantoms developed with the presented protocol exhibited physiologically relevant acoustic properties [attenuation coefficient: 0.229±0.032 dB/( [Formula: see text]) and acoustic speed: 1535±2.4 m/s], and their pulsatile flow dynamics closely resembled the flow profile input. As a first application of our developed phantoms, the flow pattern of the patient-specific aneurysm model was visualized by performing high-frame-rate color-encoded speckle imaging over multiple time-synchronized scan planes. Persistent recirculation was observed, and the vortex center was found to shift in position over a cardiac cycle, indicating the 3-D nature of flow recirculation inside an aneurysm. These findings suggest that phantoms produced from our reported protocol can serve well as acoustically compatible test beds for vascular ultrasound studies, including 3-D flow imaging.

  15. A novel mechanism of vascular relaxation induced by sodium nitroprusside in the isolated rat aorta.

    Science.gov (United States)

    Bonaventura, Daniella; Lunardi, Claure N; Rodrigues, Gerson J; Neto, Mário A; Bendhack, Lusiane M

    2008-06-01

    Sodium nitroprusside (SNP) is an endothelium-independent relaxant agent and its effect is attributed to its direct action on the vascular smooth muscle (VSM). Endothelium modulates the vascular tone through the release of vasoactive agents, such as NO. The aim of this study was to investigate the contribution of the endothelium on SNP vasorelaxation, NO release and Ca2+ mobilization. Vascular reactivity experiments showed that endothelium potentiates the SNP-relaxation in rat aortic rings and this effect was abolished by l-NAME. SNP-relaxation in intact endothelium aorta was inhibited by NOS inhibitors for the constitutive isoforms (cNOS). Furthermore, endogenous NO is involved on the SNP-effect and this endogenous NO is released by cNOS. Moreover, Ca2+ mobilization study shows that l-NAME inhibited the reduction of Ca2+-concentration in VSM cells and reduced the increase in Ca2+-concentration in endothelial cells induced by SNP. This enhancement in Ca2+-concentration in the endothelial cells is due to a voltage-dependent Ca2+ channels activation. The present findings indicate that the relaxation and [Ca2+]i decrease induced by SNP in VSM cells is potentiated by endothelial production of NO by cNOS-activation in rat aorta.

  16. The role of eNOS phosphorylation in causing drug-induced vascular injury.

    Science.gov (United States)

    Tobin, Grainne A McMahon; Zhang, Jun; Goodwin, David; Stewart, Sharron; Xu, Lin; Knapton, Alan; González, Carlos; Bancos, Simona; Zhang, Leshuai; Lawton, Michael P; Enerson, Bradley E; Weaver, James L

    2014-06-01

    Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.

  17. Characterization of ionizing radiation-induced unfolded protein response in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ju; Lee, Yoon Jin; Kang, Seong Man [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-04-15

    Misfolded or unfolded proteins within the endoplasmic reticulum (ER stress), viral infection, or amino acid deprivation induce eukaryotic translation initiation factor 2α phosphorylation (eIF2α) in eukaryotic cells, repressing global protein synthesis coincident with preferential translation of activating transcription factor 4 (ATF4). ATF4 is a transcriptional activator of genes involved in amino acid metabolism, cellular redox homeostasis, and regulation of apoptosis. When the eIF2α/ATF4 pathway is initiated by ER stress, the pathway is referred toas the unfolded protein response (UPR). In addition to DNA, proteins may be initial and important targets of ionizing radiation (IR), and the damaged protein can trigger ER stress pathway. Recent investigations suggested that IR induces ER stress followed by UPR in various cell types including intestinal epithelial cells. We conducted this study to determine whether IR can activate UPR in human vascular endothelial cells. Our data have shown that IR increased PERK-dependent eIF2α phosphorylation accompanied by induction in ATF4 protein levels in human vascular endothelial cells without alterations in expressions of XBP-1s and GRP78. Based on these data, we suggest that IR selectively activates PERK branch of unfolded protein response in human vascular endothelial cells.

  18. VEGF165-induced vascular permeability requires NRP1 for ABL-mediated SRC family kinase activation

    Science.gov (United States)

    Lampropoulou, Anastasia; Senatore, Valentina; Brash, James T.; Liyanage, Sidath E.; Raimondi, Claudio; Bainbridge, James W.

    2017-01-01

    The vascular endothelial growth factor (VEGF) isoform VEGF165 stimulates vascular growth and hyperpermeability. Whereas blood vessel growth is essential to sustain organ health, chronic hyperpermeability causes damaging tissue edema. By combining in vivo and tissue culture models, we show here that VEGF165-induced vascular leakage requires both VEGFR2 and NRP1, including the VEGF164-binding site of NRP1 and the NRP1 cytoplasmic domain (NCD), but not the known NCD interactor GIPC1. In the VEGF165-bound receptor complex, the NCD promotes ABL kinase activation, which in turn is required to activate VEGFR2-recruited SRC family kinases (SFKs). These results elucidate the receptor complex and signaling hierarchy of downstream kinases that transduce the permeability response to VEGF165. In a mouse model with choroidal neovascularisation akin to age-related macular degeneration, NCD loss attenuated vessel leakage without affecting neovascularisation. These findings raise the possibility that targeting NRP1 or its NCD interactors may be a useful therapeutic strategy in neovascular disease to reduce VEGF165-induced edema without compromising vessel growth. PMID:28289053

  19. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

  20. Transport of Brownian spheroidal nanoparticles in near-wall vascular flows for cancer therapy

    Science.gov (United States)

    Lin, Tiras Y.; Shah, Preyas N.; Smith, Bryan R.; Shaqfeh, Eric S. G.

    2016-11-01

    The microenvironment local to a tumor is characterized by a leaky vasculature induced by angiogenesis from tumor growth. Small pores form in the blood vessel walls, and these pores provide a pathway for cancer-ameliorating nanoparticle drug carriers. Using both simulations and microfluidics experiments, we investigate the extravasation of nanoparticles through pores. Using Brownian dynamics simulations, we evolve the stochastic equations for both point particles and finite-size spheroids of varying aspect ratio. We investigate the effect of wall shear flow and pore suction flow (Sampson flow) on the extravasation process. We consider pores of two types: physiologically relevant short pores with a length equal to the particle size and long pores which are relevant to diffusion through membranes. Additionally, we perform microfluidics experiments in which the extravasation rates of various nanoparticles tagged with fluorescent dye through pores are measured. In particular, using fluorometry we measure the flux of nanoparticles across a track-etched membrane, which separates two chambers. Our preliminary results indicate that the flux measured from experiment agrees reasonably with the simulations done with long pores, and we discuss the effect of pore length on extravasation. T.Y.L. is supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

  1. TGF-beta Inhibits Ang II-Induced MAPK p44/42 Signaling in Vascular Smooth Muscle Cells by Ang II Type 1 Receptor Downregulation

    NARCIS (Netherlands)

    Meijering, Bernadet D. M.; van der Wouden, Els A.; Pelgrom, Vincent; Henning, Robert H.; Sharma, Kumar; Deelman, Leo E.

    2009-01-01

    Vascular changes in diabetes are characterized by reduced vasoconstriction and vascular remodeling. Previously, we demonstrated that TGF-beta 1 impairs Ang II-induced contraction through reduced calcium mobilization. However, the effect of TGF-beta 1 on Ang II-induced vascular remodeling is unknown.

  2. Endothelium negatively modulates the vascular relaxation induced by nitric oxide donor, due to uncoupling NO synthase.

    Science.gov (United States)

    Bonaventura, Daniella; Lunardi, Claure N; Rodrigues, Gerson J; Neto, Mário A; Vercesi, Juliana A; de Lima, Renata G; da Silva, Roberto S; Bendhack, Lusiane M

    2009-10-01

    Nitrosyl ruthenium complexes have been characterized as nitric oxide (NO) donors that induce relaxation in the denuded rat aorta. There are some differences in their vascular relaxation mechanisms compared with sodium nitroprusside. This study investigates whether the endothelium could interfere with the [Ru(terpy)(bdq)NO](3+)-TERPY-induced vascular relaxation, by analyzing the maximal relaxation (Emax) and potency (pD(2)) of TERPY. Vascular reactivity experiments showed that the endothelium negatively modulates (pD(2): 6.17+/-0.07) the TERPY relaxation in intact rat aortic rings compared with the denuded rat aorta (pD(2): 6.65+/-0.07). This effect is abolished by a non-selective NO-synthase (NOS) inhibitor L-NAME (pD(2): 6.46+/-0.10), by the superoxide anion (O(2)(-)) scavenger TIRON (pD(2): 6.49+/-0.08), and by an NOS cofactor BH(4) (pD(2): 6.80+/-0.10). The selective dye for O(2)(-) (DHE) shows that TERPY enhances O(2)(-) concentration in isolated endothelial cells (intensity of fluorescence (IF):11258.00+/-317.75) compared with the basal concentration (IF: 7760.67+/-381.50), and this enhancement is blocked by L-NAME (IF: 8892.33+/-1074.41). Similar results were observed in vascular smooth muscle cells (concentration of superoxide after TERPY: 2.63+/-0.17% and after TERPY+L-NAME: -4.63+/-0.14%). Considering that TERPY could induce uncoupling NOS, thus producing O(2)(-), we have also investigated the involvement of prostanoids in the negative modulation of the endothelium. The non-selective cyclooxygenase (COX) inhibitor indomethacin and the selective tromboxane (TXA(2)) receptor antagonist SQ29548 reduce the effect of the endothelium on TERPY relaxation (pD(2) INDO: 6.80+/-0.17 and SQ29548: 6.85+/-0.15, respectively). However, a selective prostaglandin F(2alpha) receptor antagonist (AH6809) does not change the endothelium effect. Moreover, TERPY enhances the concentration of TXA(2) stable metabolite (TXB(2)), but this effect is blocked by L-NAME and TIRON. The

  3. Three-dimensional vascular network assembly from diabetic patient-derived induced pluripotent stem cells

    Science.gov (United States)

    Chan, Xin Yi; Black, Rebecca; Dickerman, Kayla; Federico, Joseph; Levesque, Mathieu; Mumm, Jeff; Gerecht, Sharon

    2015-01-01

    Objective In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer three-dimensional (3D) vascular networks in synthetic hydrogels from type-1 diabetes (T1D) patient-derived human induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. Approach and Results We validated and optimized an adherent, feeder free differentiation procedure to derive early vascular cells (EVCs) with high portions of VEcad+ cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and T1D patients. T1D-hiPSC-derived VEcad+ cells can mature to functional endothelial cells (ECs) expressing mature markers: von Willebrand factor and eNOS, are capable of lectin binding and acetylated low density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor alpha. When embedded in engineered hyaluronic acid (HA) hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible (HI) hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. Conclusion Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early ECs derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in HA and HI hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering. PMID:26449749

  4. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling

    Directory of Open Access Journals (Sweden)

    Angelini Daniel J

    2013-01-01

    Full Text Available Abstract Background Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in explaining this differential response. Methods We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung. Results Chronic hypoxia increased both mean pulmonary artery pressure (mPAP and right ventricular (RV hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue. Conclusions The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.

  5. Cooperative effect of roscovitine and irradiation targets angiogenesis and induces vascular destabilization in human breast carcinoma.

    Science.gov (United States)

    Maggiorella, L; Aubel, C; Haton, C; Milliat, F; Connault, E; Opolon, P; Deutsch, E; Bourhis, J

    2009-02-01

    Angiogenesis is considered as an essential process for tumour development and invasion. Previously, we demonstrated that cyclin-dependent kinase inhibition by roscovitine induces a radiosensitization and a synergistic antitumoral effect in human carcinoma but its effect on the microenvironment and tumour angiogenesis remains unknown. Here, we investigated the effect of the combination roscovitine and ionizing radiation (IR) on normal cells in vitro and on tumour angiogenesis in MDA-MB 231 tumour xenografts. We observed that the combination roscovitine and IR induced a marked reduction of angiogenic hot spot and microvascular density in comparison with IR or roscovitine treatments alone. The Ang-2/Tie-2 ratio was increased in presence of reduced vascular endothelial growth factor level suggesting vessel destabilization. In vitro, no radiosensitization effect of roscovitine was found in endothelial, fibroblast, and keratinocyte cells. IR potentiated the antiproliferative effect of roscovitine without inducing apoptosis in endothelial cells. Roscovitine decreased IR-stimulated vascular endothelial growth factor secretion of MDA-MB 231 and endothelial cells. A reduction in the endothelial cells invasion and the capillary-like tube formation in Matrigel were observed following the combination roscovitine and IR. This combined treatment targets angiogenesis resulting in microvessel destabilization without inducing normal cell toxicity.

  6. Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity.

    Science.gov (United States)

    Rossman, Matthew J; Groot, H Jonathan; Garten, Ryan S; Witman, Melissa A H; Richardson, Russell S

    2016-11-01

    The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA (r = 0.57 and r = 0.66) and SFA (r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA (r = 0.38 and r = 0.35) and SFA (r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.

  7. Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Xiao PANG; Ning-ling SUN

    2009-01-01

    Aim: Catecholamine-induced vascular smooth muscle cell (VSMC) proliferation is one of the major events in the pathogenesis of atherosclerosis and vascular remodeling. The calcineurin-NFAT pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the calcineurin-NFAT pathway was involved in the regulation of phenylephrine-induced VSMC proliferation.Methods: Proliferation of VSMC was measured using an MTT assay and cell counts. Localization of NFATcl was detected by immunofluorescence staining. NFATcl-DNA binding was determined by EMSA and luciferase activity analyses.NFATcl and calcineurin levels were assayed by immunoprecipitation.Results: Phenylephrine (PE, an α1-adrenoceptor agonist) increased VSMC proliferation and cell number. Prazosin (an α1-adrenoceptor antagonist), cyclosporin A (CsA, an inhibitor of calcineurin) and chelerythrine (an inhibitor of PKC)decreased PE-induced proliferation and cell number. Additional treatment of VSMC with CsA or chelerythrine further inhibited proliferation and cell number in the chelerythrine-pretreatment group and the CsA-pretreatment group. CsA and chelerythrine alone had no effect on either absorbance or cell number. CsA decreased PE-induced calcineurin levels and activity. NFATc1 was translocated from the cytoplasm to the nucleus upon treatment with PE. This translocation was reversed by CsA. CsA decreased the PE-induced NFATc1 level in the nucleus. PE increased NFAT's DNA binding activity and NFAT-dependent reporter gene expression. CsA blocked these effects.Conclusion: CsA partially suppresses PE-induced VSMC proliferation by inhibiting calcineurin activity and NFATc1 nuclear translocation. The calcineurin-NFATc1 pathway is involved in the hyperplastic growth of VSMC induced by phenylephrine.

  8. Decrease of synaptic plasticity associated with alteration of information flow in a rat model of vascular dementia.

    Science.gov (United States)

    Xu, X; Li, Z; Yang, Z; Zhang, T

    2012-03-29

    This investigation examined whether the directional index of neural information flow (NIF) could be employed to characterize the synaptic plasticity in the CA3-CA1 pathway of the hippocampus and assessed which oscillatory rhythm was associated with cognitive impairments induced by vascular dementia (VD). Rats were randomly divided into control and VD groups. The animal model of VD used the two-vessel occlusion (2VO) method. Behavior was measured using the Morris water maze (MWM). Local field potentials (LFPs) from CA3 and CA1 were recorded after behavioral tests, followed by recording long-term potentiation (LTP) of the same CA3-CA1 pathway. General partial directed coherence (gPDC) approach was utilized to determine the directionality of NIF between CA3 and CA1 over five frequency bands, which were delta, theta, alpha, beta, and gamma. The results showed that the escape latencies were significantly prolonged in the VD group, whereas the swimming speeds of these two groups remained constant throughout testing. Moreover, the phase synchronization values between CA3 and CA1 regions were reduced in theta, alpha, beta, and gamma bands in the VD state compared to that in the normal state. The coupling directional index was considerably decreased in the previously given four frequency bands in VD rats, whereas the strength of CA3 driving CA1 was significantly reduced in the same frequency bands. Interestingly, LTP was significantly decreased in the VD group, which was consistent with the LFPs findings. The data suggest that the directionality index of NIF in these physiological oscillatory rhythms could be used as a measure of synaptic plasticity in the hippocampal CA3-CA1 pathway in VD states. The potential mechanism of the relationship between NIF direction and synaptic plasticity in VD state was discussed.

  9. Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles.

    Science.gov (United States)

    Siyahhan, Bercan; Knobloch, Verena; de Zélicourt, Diane; Asgari, Mahdi; Schmid Daners, Marianne; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2014-05-06

    While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation.

  10. Antagonism of Stem Cell Factor/c-kit Signaling Attenuates Neonatal Chronic Hypoxia-Induced Pulmonary Vascular Remodeling

    Science.gov (United States)

    Young, Karen C; Torres, Eneida; Hehre, Dorothy; Wu, Shu; Suguihara, Cleide; Hare, Joshua M.

    2015-01-01

    Background Accumulating evidence suggests that c-kit positive cells are present in the remodeled pulmonary vasculature bed of patients with pulmonary hypertension (PH). Whether stem cell factor (SCF)/ c-kit regulated pathways potentiate pulmonary vascular remodeling is unknown. Here, we tested the hypothesis that attenuated c-kit signaling would decrease chronic hypoxia-induced pulmonary vascular remodeling by decreasing pulmonary vascular cell mitogenesis. Methods Neonatal FVB/NJ mice treated with non-immune IgG (PL), or c-kit neutralizing antibody (ACK2) as well as c-kit mutant mice (WBB6F1- Kit W− v/ +) and their congenic controls, were exposed to normoxia (FiO2=0.21) or hypoxia (FiO2=0.12) for two weeks. Following this exposure, right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), pulmonary vascular cell proliferation and remodeling were evaluated. Results As compared to chronically hypoxic controls, c-kit mutant mice had decreased RVSP, RVH, pulmonary vascular remodeling and proliferation. Consistent with these findings, administration of ACK2 to neonatal mice with chronic hypoxia-induced PH decreased RVSP, RVH, pulmonary vascular cell proliferation and remodeling. This attenuation in PH was accompanied by decreased extracellular signal-regulated protein kinase (ERK) 1/2 activation. Conclusion SCF/c-kit signaling may potentiate chronic hypoxia-induced vascular remodeling by modulating ERK activation. Inhibition of c-kit activity may be a potential strategy to alleviate PH. PMID:26705118

  11. Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2016-10-01

    Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia.

  12. Escleroterapia con bleomicina en malformaciones vasculares de bajo flujo: Experiencia y revisión del tema Bleomycin sclerotherapy for low-flow vascular malformations: our experience and literature review

    Directory of Open Access Journals (Sweden)

    F. Lobo Bailón

    2012-12-01

    Full Text Available Las anomalías vasculares son lesiones típicas de los pacientes pediátricos y se dividen en dos categorías: tumores vasculares y malformaciones vasculares de alto y bajo flujo. Estas últimas pueden tratarse de diversos modos: laserterapia, drenaje, aspiración, cirugía o escleroterapia, dependiendo del tipo de lesión y de su localización. Entre los agentes esclerosantes utilizados, la bleomicina ha demostrado tener buenos resultados en el tratamiento de estas lesiones. En este artículo presentamos nuestra experiencia en el tratamiento de las malformaciones vasculares de bajo flujo mediante escleroterapia con bleomicina intralesional. Desarrollamos un estudio descriptivo retrospectivo sobre 30 pacientes que presentaban malformación vascular de bajo flujo y fueron tratados con bleomicina intralesional. Los resultados fueron buenos o excelentes en 22 pacientes y regulares o malos en los 8 restantes. De acuerdo a nuestra casuística y a la literatura revisada, la escleroterapia con bleomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las malformaciones vasculares de bajo flujo.Vascular anomalies are common in children and can be divided into two categories, vascular tumours and vascular malformations: high-flow or low-flow. The latter can be treated in different ways such as lasertherapy, drainage, aspiration, surgery or sclerotherapy depending on the type and location of the lesion. Among the accepted sclerosing agents, bleomycin has proven good results in the treatment of this condition. Herein we present our experience in the treatment of low-flow vascular malformations with intralesional bleomycin injection. This is a retrospective, descriptive study with 30 patients presenting a low-flow vascular malformation treated with intralesional bleomycin injection. Our results are good or excellent in 22 patients and poor in the other 8. According to our case series and the consulted literature, sclerotherapy with

  13. Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS

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    Sheepsumon Viboolvorakul

    2014-01-01

    Full Text Available This study aimed to investigate the effect of exercise training on age-induced microvascular alterations in the brain. Additionally, the association with the protein levels of vascular endothelial growth factor (VEGF and endothelial nitric oxide synthase (eNOS was also assessed. Male Wistar rats were divided into four groups: sedentary-young (SE-Young, n=5, sedentary aged (SE-Aged, n=8, immersed-aged (IM-Aged, n=5, and exercise trained-aged (ET-Aged, 60 minutes/day and 5 days/week for 8 weeks, n=8 rats. The MAPs of all aged groups, SE-Aged, IM-Aged, and ET-Aged, were significantly higher than that of the SE-Young group. The regional cerebral blood flow (rCBF in the SE-Aged and IM-Aged was significantly decreased as compared to SE-Young groups. However, rCBF of ET-Aged group was significantly higher than that in the IM-Aged group (P<0.05. Moreover, the percentage of capillary vascularity (%CV and the levels of VEGF and eNOS in the ET-Aged group were significantly increased compared to the IM-Aged group (P<0.05. These results imply that exercise training could improve age-induced microvascular changes and hypoperfusion closely associated with the upregulation of VEGF and eNOS.

  14. Roscovitine inhibits ERK1/2 activation induced by angiotensin II in vascular smooth muscle cells.

    Science.gov (United States)

    Li, Ai-Ying; Han, Mei; Zheng, Bin; Wen, Jin-Kun

    2008-01-23

    Roscovitine is a potent CDK inhibitor often used as a biological tool in cell-cycle studies, but its working mechanism and real targets in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we observed that ERK1/2 phosphorylation induced by Ang II was abrogated by pretreating VSMCs with roscovitine for 15h. Pretreating VSMCs with roscovitine also inhibited Ang II-induced c-Jun expression and phosphorylation. We further demonstrated that roscovitine could suppress the DNA binding activity of c-Jun and activation of angiotensinogen promoter by Ang II. These results suggest that roscovitine represses Ang II-induced angiotensinogen expression by inhibiting activation of ERK1/2 and c-Jun.

  15. ExoU-induced vascular hyperpermeability and platelet activation in the course of experimental Pseudomonas aeruginosa pneumosepsis.

    Science.gov (United States)

    Machado, Gloria-Beatriz S; de Assis, Maria-Cristina; Leão, Robson; Saliba, Alessandra M; Silva, Mauricio C A; Suassuna, Jose H; de Oliveira, Albanita V; Plotkowski, Maria-Cristina

    2010-03-01

    To address the question whether ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, can induce hemostatic abnormalities during the course of pneumosepsis, mice were instilled i.t. with the ExoU-producing PA103 P. aeruginosa or with a mutant obtained by deletion of the exoU gene. Control animals were instilled with sterile vehicle. To assess the role of ExoU in animal survival, mice were evaluated for 72 h. In all the other experiments, animals were studied at 24 h after infection. PA103-infected mice showed significantly higher mortality rate, lower blood leukocyte concentration, and higher platelet concentration and hematocrit than animals infected with the bacterial mutant, as well as evidences of increased vascular permeability and plasma leakage, which were confirmed by our finding of higher protein concentration in bronchoalveolar lavage fluids and by the Evans blue dye assay. Platelets from PA103-infected mice demonstrated features of activation, assessed by the flow cytometric detection of higher percentage of P-selectin expression and of platelet-derived microparticles as well as by the enzyme immunoassay detection of increased thromboxane A2 concentration in animal plasma. Histopathology of lung and kidney sections from PA103-infected mice exhibited evidences of thrombus formation that were not detected in sections of animals from the other groups. Our results demonstrate the ability of ExoU to induce vascular hyperpermeability, platelet activation, and thrombus formation during P. aeruginosa pneumosepsis, and we speculate that this ability may contribute to the reported poor outcome of patients with severe infection by ExoU-producing P. aeruginosa.

  16. Flow-induced vibrations of circular cylindrical structures. [LMFBR

    Energy Technology Data Exchange (ETDEWEB)

    Chen, S.

    1977-06-01

    The problems of flow-induced vibrations of circular cylindrical structures are reviewed. First, the general method of analysis and classification of structural responses are presented. Then, the presentation is broken up along the lines with stationary fluid, parallel flow, and cross flow. Finally, design considerations and future research needs are pointed out. 234 references.

  17. Role of endogenous nitric oxide on PAF-induced vascular and respiratory effects

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    M. Clement

    1995-01-01

    Full Text Available The role of endogenous nitric oxide (NO on vascular and respiratory smooth muscle basal tone was evaluated in six anaesthetized, paralysed, mechanically ventilated pigs. The involvement of endogenous NO in PAF-induced shock and airway hyperresponsiveness was also studied. PAF (50 ng/kg, i.v. was administered before and after pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., an NO synthesis inhibitor. PAF was also administered to three of these pigs after indomethacin infusion (3 mg/kg, i.v.. In normal pigs, L-NAME increased systemic and pulmonary vascular resistances, caused pulmonary hypertension and reduced cardiac output and stroke volume. The pulmonary vascular responses were correlated with the increase in static and dynamic lung elastances, without changing lung resistance. Inhibition of NO synthesis enhanced the PAF-dependent increase in total, intrinsic and viscoelastic lung resistances, without affecting lung elastances or cardiac activity. The systemic hypotensive effect of PAF was not abolished by pretreatment with L-NAME or indomethacin. This indicates that systemic hypotension is not correlated with the release of endogenous NO or prostacyclines. Indomethacin completely abolished the PAF-dependent respiratory effects.

  18. Mitochondrial aldehyde dehydrogenase prevents ROS-induced vascular contraction in angiotensin-II hypertensive mice.

    Science.gov (United States)

    Choi, Hyehun; Tostes, Rita C; Webb, R Clinton

    2011-01-01

    Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme that detoxifies aldehydes to carboxylic acids. ALDH2 deficiency is known to increase oxidative stress, which is the imbalance between reactive oxygen species (ROS) generation and antioxidant defense activity. Increased ROS contribute to vascular dysfunction and structural remodeling in hypertension. We hypothesized that ALDH2 plays a protective role to reduce vascular contraction in angiotensin-II (AngII) hypertensive mice. Endothelium-denuded aortic rings from C57BL6 mice, treated with AngII (3.6 μg/kg/min, 14 days), were used to measure isometric force development. Rings treated with daidzin (10 μmol/L), an ALDH2 inhibitor, potentiated contractile responses to phenylephrine (PE) in AngII mice. Tempol (1 mmol/L) and catalase (600 U/mL) attenuated the augmented contractile effect of daidzin. In normotensive mice, contraction to PE in the presence of the daidzin was not different from control, untreated values. AngII aortic rings transfected with ALDH2 recombinant protein decreased contractile responses to PE compared with control. These data suggest that ALDH2 reduces vascular contraction in AngII hypertensive mice. Because tempol and catalase blocked the contractile response of the ALDH2 inhibitor, ROS generation by AngII may be decreased by ALDH2, thereby preventing ROS-induced contraction.

  19. Lanthanum acetate inhibits vascular calcification induced by vitamin D3 plus nicotine in rats.

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    Zhou, Ye-Bo; Jin, Shao-Ju; Cai, Yan; Teng, Xu; Chen, Li; Tang, Chao-Shu; Qi, Yong-Fen

    2009-08-01

    Lanthanum, a rare earth element, has been used to decrease serum phosphorus level in patients with chronic renal disease and hyperphosphatemia. We aimed to observe the effect and mechanism of two doses of lanthanum acetate (375 and 750 mg/kg/day) on vascular calcification induced by vitamin D3 plus nicotine treatment in rats for 4 weeks. As compared with control rats, rats with calcification showed widespread calcified nodules and irregular elastic fibers in calcified aorta on von Kossa calcium staining and increased aortic calcium and phosphorus contents, alkaline phosphatase (ALP) activity and bone-related protein expressions for osteopontin (OPN) and type III sodium dependent phosphate cotransporter Pit-1 (Pit-1). After treatment with either dose of lanthanum acetate, the calcified nodules and degree of irregular elastic fibers decreased in aortas. Lanthanum acetate at 750 mg/kg/day was more effective than 375 mg/kg/day in lessening vascular calcification by significantly reducing plasma phosphorus level, calcium x phosphorus product and ALP activity, by 30.3%, 28.6%, and 68.6%, respectively; reducing aortic phosphorus and calcium contents and ALP activity, by 48%, 53.1%, and 63.5% (all P nicotine alone. Lanthanum acetate could effectively inhibit the pathogenesis of vascular calcification.

  20. Fatty acid-induced changes in vascular reactivity in healthy adult rats.

    Science.gov (United States)

    Christon, Raymond; Marette, André; Badeau, Mylène; Bourgoin, Frédéric; Mélançon, Sébastien; Bachelard, Hélène

    2005-12-01

    Dietary fatty acids (FAs) are known to modulate endothelial dysfunction, which is the first stage of atherosclerosis. However, their exact role in this initial phase is still unclear. The effects of isolated or combined (by 2) purified FAs from the main FA families were studied on the vascular response of isolated thoracic aorta in healthy rats to get a better understanding of the mechanisms of action of dietary FAs in regulating vascular endothelial function. Cumulative contraction curves to phenylephrine and relaxation curves to carbachol and then to sodium nitroprusside were obtained in the absence or presence of the FAs studied allowing endothelium-dependent and endothelium-independent ability of the smooth muscle to relax to be assessed in each experimental group. The endothelium-dependent vasodilator response to carbachol was lowered by eicosapentaenoic acid, whereas it was not altered either by docosahexaenoic acid alone or by combined eicosapentaenoic acid-docosahexaenoic acid, oleic acid, or stearic acid, and it was increased by linoleic acid (LA). A decreased phenylephrine-induced contraction was observed after incubation with arachidonic acid and with stearic acid. On the other hand, the endothelium-dependent relaxation was reduced by the addition of combined LA-arachidonic acid and LA-oleic acid. In conclusion, these data point out the differential effects of different types of FAs and of FAs alone vs combined on vascular reactivity. The complex nature of these effects could be partially linked to metabolic specificities of endothelial cells and to interactions between some FAs.

  1. A new in vitro model to delay high phosphate-induced vascular calcification progression.

    Science.gov (United States)

    Ciceri, Paola; Elli, Francesca; Cappelletti, Laura; Tosi, Delfina; Braidotti, Paola; Bulfamante, Gaetano; Cozzolino, Mario

    2015-12-01

    An increasing amount of patients affected by advanced chronic kidney disease suffer from vascular calcification (VC) that associates with cardiovascular morbidity and mortality. In this study, we created a new experimental in vitro model, trying to better elucidate high phosphate (Pi)-induced VC pathogenic mechanisms. Rat aortic vascular smooth muscle cells (VSMCs) were challenged for 7-10 days with high Pi with a repeated and short suspensions of high Pi treatment (intermittent suspension, IS) that was able to induce a significant inhibition of high Pi calcification, maximal at 5 h. Interestingly, the delay in calcification is a consequence of either the absence of free Pi or calcium-phosphate crystals being comparable to the total effect obtained during the 5 h-IS. The protective effect of IS was mediated by the reduction of apoptosis as demonstrated by the action of 20 μmol/L Z-VAD-FMK and by the preservation of the pro-survival receptor Axl expression. Furthermore, autophagy, during IS, was potentiated by increasing the autophagic flux, evaluated by LC3IIB western, while treating VSMCs with 1 mmol/L valproic acid did not affect VC. Finally, IS prevented VSMC osteoblastic differentiation by preserving smooth muscle lineage markers expression. Our data support the hypothesis that to delay significantly VC is necessary and sufficient the IS of high Pi challenge. The IS was able to prevent significantly apoptosis, to induce a potentiation in autophagy, and to prevent osteoblastic differentiation by preserving SM lineage markers.

  2. Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

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    Shen Junhui

    2012-07-01

    Full Text Available Abstract Background Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3 and eicosapentaenoic acid (EPA, 20:5 ω-3. The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. Methods RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF secretion were evaluated. Results Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA and α-linolenic acid (ALA, while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed

  3. Experimental study of icariin on vascular dementia in rats induced by 2-VO method

    Institute of Scientific and Technical Information of China (English)

    Rui-xiaXU; QinWU; Jing-shanSHI

    2004-01-01

    AIM: To study the effects of icariin (ICA) on the learning and memory of ischemic vascular dementia (VD) model of rats,and explore the protective mechanisms. METHODS: ICA was administered to the VD model rats induced by a permanent bilateral occlusion of both common carotids arteries(2-VO method) and by cerebral ischemia-reperfusion (I10-R 10-110 method). Morris water maze was used to examine the abilities of spatial learning and memory of VD model rats. The activity of SOD, level of

  4. Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension

    Science.gov (United States)

    GOODWIN, Julie E.; ZHANG, Junhui; GONZALEZ, David; ALBINSSON, Sebastian; GELLER, David S.

    2012-01-01

    Glucocorticoid-mediated hypertension is incompletely understood. Recent studies have suggested the primary mechanism of this form of hypertension may be through the effects of glucocorticoids on vascular tissues and not to excess sodium and water reabsorption as traditionally believed. Objective The goal of this study was to better understand the role of the vasculature in the generation and maintenance of glucocorticoid-mediated hypertension. Methods We created a mouse model with a tissue-specific knockout of the glucocorticoid receptor in the vascular endothelium. Results We show that these mice are relatively resistant to dexamethasone-induced hypertension. After one week of dexamethasone treatment, control animals have a mean blood pressure increase of 13.1 mm Hg while knockout animals have only a 2.7 mm Hg increase (p<0.001). Interestingly, the knockout mice have slightly elevated baseline BP compared to the controls (112.2 ± 2.5 mm Hg vs. 104.6 ± 1.2 mm Hg, p = 0.04), a finding which is not entirely explained by our data. Furthermore, we demonstrate that the knockout resistance arterioles have a decreased contractile response to dexamethasone with only 6.6% contraction in knockout vessels compared to 13.4% contraction in control vessels (p=0.034). Finally, we show that in contrast to control animals, the knockout animals are able to recover a significant portion of their normal circadian blood pressure rhythm suggesting that the vascular endothelial glucocorticoid receptor may function as a peripheral circadian clock. Conclusions Our study highlights the importance of the vascular endothelial GR in several fundamental physiologic processes, namely blood pressure homeostasis and circadian rhythm. PMID:21659825

  5. Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

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    Raja Kumar Vadivelu

    2012-01-01

    Full Text Available Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05. Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC.

  6. Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model.

    Science.gov (United States)

    Basralı, Filiz; Koçer, Günnur; Ülker Karadamar, Pınar; Nasırcılar Ülker, Seher; Satı, Leyla; Özen, Nur; Özyurt, Dilek; Şentürk, Ümit Kemal

    2015-01-01

    The aim of this study was to assess the effect of oral magnesium supplementation (Mg-supp) on blood pressure (BP) and possible mechanism in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension and/or Mg-supp were created by N-nitro-l-arginine methyl ester (25 mg/kg/day by drinking water) and magnesium-oxide (0.8% by diet) for 6 weeks. Systolic BP was measured weekly by tail-cuff method. The effects of hypertension and/or Mg-supp in thoracic aorta and third branch of mesenteric artery constriction and relaxation responses were evaluated. NOS-inhibition produced a gradually developing hypertension and the magnitude of the BP was significantly attenuated after five weeks of Mg-supp. The increased phenylephrine-induced contractile and decreased acetylcholine (ACh)-induced dilation responses were found in both artery segments of hypertensive groups. Mg-supp was restored ACh-relaxation response in both arterial segments and also Phe-constriction response in thoracic aorta but not in mesenteric arteries. The contributions of NO, prostaglandins and K(+) channels to the dilator response of ACh were similar in the aorta of all the groups. The contribution of the NO to the ACh-mediated relaxation response of mesenteric arteries was suppressed in hypertensive rats, whereas this was corrected by Mg-supp. The flow-mediated dilation response of mesenteric arteries in hypertensive rats failed and could not be corrected by Mg-supp. Whereas, vascular eNOS protein and magnesium levels were not changed and plasma nitrite levels were reduced in hypertensive rats. The results of this study showed that Mg-supp lowered the arterial BP in NOS-inhibition induced hypertension model by restoring the agonist-induced relaxation response of the arteries.

  7. Brazilin Ameliorates High Glucose-Induced Vascular Inflammation via Inhibiting ROS and CAMs Production in Human Umbilical Vein Endothelial Cells

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    Thanasekaran Jayakumar

    2014-01-01

    Full Text Available Vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Recent studies have shown that brazilin exhibits antihepatotoxic, antiplatelet, cancer preventive, or anti-inflammatory properties. Thus, we investigated whether brazilin suppresses vascular inflammatory process induced by high glucose (HG in cultured human umbilical vein endothelial cells (HUVEC. HG induced nitrite production, lipid peroxidation, and intracellular reactive oxygen species formation in HUVEC cells, which was reversed by brazilin. Western blot analysis revealed that brazilin markedly inhibited HG-induced phosphorylation of endothelial nitric oxide synthase. Besides, we investigated the effects of brazilin on the MAPK signal transduction pathway because MAPK families are associated with vascular inflammation under stress. Brazilin blocked HG-induced phosphorylation of extracellular signal-regulated kinase and transcription factor NF-κB. Furthermore, brazilin concentration-dependently attenuated cell adhesion molecules (ICAM-1 and VCAM-1 expression induced by various concentrations of HG in HUVEC. Taken together, the present data suggested that brazilin could suppress high glucose-induced vascular inflammatory process, which may be closely related with the inhibition of oxidative stress, CAMs expression, and NF-κB activation in HUVEC. Our findings may highlight a new therapeutic intervention for the prevention of vascular diseases.

  8. Flow induced streamer formation in particle laden complex flows

    Science.gov (United States)

    Debnath, Nandini; Hassanpourfard, Mahtab; Ghosh, Ranajay; Trivedi, Japan; Thundat, Thomas; Kumar, Aloke

    2016-11-01

    We study the combined flow of a polyacrylamide (PAM)solution with polystyrene (PS) nanoparticles, through a microfluidic device containing an array of micropillars. The flow is characterized by a very low Reynolds number (Re= 20), PS nanoparticles localize near pillar walls to form thin slender string-like structures, which we call 'streamers' due to their morphology. Post-formation, these streamers show significant viscous behavior for short observational time-scales, and at longer observational time scales elastic response dominates. Our abiotic streamers could provide a framework for understanding similar structures that often form in biological systems. PhD student, Department of Mechanical Engineering.

  9. Crucial role of androgen receptor in vascular H2S biosynthesis induced by testosterone.

    Science.gov (United States)

    Brancaleone, V; Vellecco, V; Matassa, D S; d'Emmanuele di Villa Bianca, R; Sorrentino, R; Ianaro, A; Bucci, M; Esposito, F; Cirino, G

    2015-03-01

    Hydrogen sulphide (H2S) is a gaseous mediator strongly involved in cardiovascular homeostasis, where it provokes vasodilatation. Having previously shown that H2 S contributes to testosterone-induced vasorelaxation, here we aim to uncover the mechanisms underlying this effect. H2 S biosynthesis was evaluated in rat isolated aortic rings following androgen receptor (NR3C4) stimulation. Co-immunoprecipitation and surface plasmon resonance analysis were performed to investigate mechanisms involved in NR3C4 activation. Pretreatment with NR3C4 antagonist nilutamide prevented testosterone-induced increase in H2S and reduced its vasodilator effect. Androgen agonist mesterolone also increased H2S and induced vasodilatation; effects attenuated by the selective cystathionine-γ lyase (CSE) inhibitor propargylglycine. The NR3C4-multicomplex-derived heat shock protein 90 (hsp90) was also involved in this effect; its specific inhibitor geldanamycin strongly reduced testosterone-induced H2S production. Neither progesterone nor 17-β-oestradiol induced H2S release. Furthermore, we demonstrated that CSE, the main vascular H2S-synthesizing enzyme, is physically associated with the NR3C4/hsp90 complex and the generation of such a ternary system represents a key event leading to CSE activation. Finally, H2S levels in human blood collected from male healthy volunteers were higher than those in female samples. We demonstrated that selective activation of the NR3C4 is essential for H2S biosynthesis within vascular tissue, and this event is based on the formation of a ternary complex between cystathionine-γ lyase, NR3C4and hsp90. This novel molecular mechanism operating in the vasculature, corroborated by higher H2S levels in males, suggests that the L-cysteine/CSE/H2S pathway may be preferentially activated in males leading to gender-specific H2S biosynthesis. © 2014 The British Pharmacological Society.

  10. Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

    Science.gov (United States)

    Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

    2015-12-01

    Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue.

  11. Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout muce

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis,postangioplasty restenosis and transplant arteriopathy.Recently,pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis.But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not Vet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene (LDL-/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL-/-mice with the GFP-expressing transgenic mice. LDL-/- mice (22-24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice.Four weeks later,a nonconstrictive cuff was Dlaced around the right femoral artery.After another 2 weeks,both right and left femoral arteries were harvested and subjected to histochemical analysis.Apoptosis was analyzed in situ using TUNEL assay.Resuits Two weeks after cuff placement,atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells, The tissue stained with anti-α smooth muscle actin (SMA) antibody,showed a number of SMA-positive cells in the intimal lesion area.They were also positive for GFP,indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions.Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP.The intima and media showed a larae number of TUNEL-positive signals after 2 weeks cuff injury,indicating the presence of apoptosis in vascular remodelina.Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular inJury under the hypercholesterolemic conditions

  12. Rho kinase inhibitor fasudil mitigates high-cholesterol diet-induced hypercholesterolemia and vascular damage.

    Science.gov (United States)

    Abdali, Nibrass Taher; Yaseen, Awny H; Said, Eman; Ibrahim, Tarek M

    2017-04-01

    The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2.5 mg/kg/day) starting from the ninth week for further 4 weeks with interruption of the cholesterol-rich chow. Biochemical assessment of serum cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and myocardial oxidative/antioxidant biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), besides biochemical assessment of serum nitric oxide (NO), creatine kinase (CK), and lactate dehydrogenase (LDH) activities and serum total antioxidant capacity (TAC), was conducted. Serum vascular cell adhesion molecule 1 (VCAM-1) and serum Rho-associated protein kinase 1 (ROCK-1) were also evaluated along with histopathological examination of aorta specimens. Fasudil administration significantly decreased serum cholesterol, triglyceride (TG), and LDL and significantly increased serum HDL, with concomitant decrease in serum CK and LDH activities, NO, and restoration of serum TAC. Myocardial MDA significantly declined; SOD activity and GSH contents were restored. Serum ROCK-1 and VCAM-1 levels significantly declined as well. Vascular improvement was confirmed with histopathological examination, which revealed normal aortic intema with the absence of atheromas. Fasudil has promising anti-atherogenic activity mediated primarily via alleviation of hypercholesterolemia-induced oxidative stress and modulation of inflammatory response.

  13. Panax ginseng and salvia miltiorrhiza supplementation abolishes eccentric exercise-induced vascular stiffening: a double-blind randomized control trial.

    Science.gov (United States)

    Lin, Hsin-Fu; Tung, Kang; Chou, Chun-Chung; Lin, Ching-Che; Lin, Jaung-Geng; Tanaka, Hirofumi

    2016-06-06

    Muscle damage induced by unaccustomed or eccentric exercise results in delayed onset vascular stiffening. We tested the hypothesis that a 7-day supplementation of panax ginseng and salvia miltiorrhiza prior to an acute eccentric exercise could attenuate arterial stiffening. By using a double-blind study placebo-controlled randomized design, subjects were randomly assigned to either the Chinese herb (N = 12) or the placebo group (N = 11) and performed a downhill running (eccentric exercise) trial and a control (seated rest) trial. Muscle soreness increased 1-2 days after exercise similarly in both groups, whereas the herb group demonstrated a faster recovery on active range of motion. Plasma creatine kinase concentration increased significantly at 24 h in both groups but the magnitude of increase was attenuated in the herb group. Arterial stiffness as measured by carotid-femoral pulse wave velocity increased significantly at 24 h in the placebo group but such increase was absent in the herb group. Flow-mediated dilation did not change in either group. Plasma concentrations of CRP and IL-6 increased in the placebo group but no such increases were observed in the herb group. Changes in arterial stiffness induced by eccentric exercise were associated with the corresponding changes in IL-6 (r = 0.46, P exercise. ClinicalTrials.gov: NCT02007304. Registered Dec. 5, 2013).

  14. Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

    Directory of Open Access Journals (Sweden)

    Brunner Sabine

    2011-10-01

    Full Text Available Abstract Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF. Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28% or a high-salt diet (5.5% starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food (ZDF+S+E, hydralazine (25 mg/kg per day (ZDF+S+H, or no treatment (ZDF+S. Rats on normal salt-diet were assigned to eplerenone (ZDF+E or no treatment (ZDF. Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL or high-salt diet (ZL+S serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio and vascular stiffness (strain and stress were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition

  15. Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Ruifrok, Willem-Peter T.; Voors, Adriaan A.; Tilton, Ronald G.; van Veldhuisen, Dirk J.; Schoemaker, Regien G.; van Gilst, Wiek H.; de Boer, Rudolf A.

    2010-01-01

    We intended to delineate the mechanisms of erythropoietin (EPO)-induced cardiac vascular endothelial growth factor (VEGF) production and to establish if VEGF is crucial for EPO-induced improvement of cardiac performance. The effects of EPO on VEGF expression were studied in cultured cardiac cells an

  16. Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Ruifrok, Willem-Peter T.; Voors, Adriaan A.; Tilton, Ronald G.; van Veldhuisen, Dirk J.; Schoemaker, Regien G.; van Gilst, Wiek H.; de Boer, Rudolf A.

    2010-01-01

    We intended to delineate the mechanisms of erythropoietin (EPO)-induced cardiac vascular endothelial growth factor (VEGF) production and to establish if VEGF is crucial for EPO-induced improvement of cardiac performance. The effects of EPO on VEGF expression were studied in cultured cardiac cells an

  17. Flow induced charging of liquids in reduced gravity

    Energy Technology Data Exchange (ETDEWEB)

    Pettit, D.R.

    1996-02-01

    Microgravity experiments on free fluid surfaces of large length scale could be subject to experimental artifact from flow induced charging. Under conditions favorable for flow induced charging, flowing liquids develop a static electrical charge which manifests itself as a force whose magnitude approaches that of surface tension force. Favorable conditions are: a non-conducting liquid, a small diameter non-conducting flow passage, a large flow volume, and a small separation distance between the fluid and another object. We present a method for calculating the magnitude of flow induced charging and scaling arguments so that potential problems can be determined and dealt with at the experimental design phase. A dimensionless ratio of charge force to surface tension force we call the Hula Number should be less than 0.5 to prevent artifact or unwanted fluid motion.

  18. Inhibitive effects of anti-oxidative vitamins on mannitol-induced apoptosis of vascular endothelial cells.

    Science.gov (United States)

    Pan, Kai-yu; Shen, Mei-ping; Ye, Zhi-hong; Dai, Xiao-na; Shang, Shi-qiang

    2006-10-01

    Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was performed with normal saline (group B), vitamin C (group C) and vitamin E (group D). Blood vessel injury was assessed under electron and light microscopy. In a second experiment, cell culture specimen of human umbilical vein endothelial cells were treated with mannitol. Pre-treatment was done with normal saline (sample B), vitamin C (sample C) and vitamin E (sample D). Total RNA was extracted with the original single step procedure, followed by hybridisation and analysis of gene expression. In the animal experiment, serious blood vessel injury was seen in group A and group B. Group D showed light injury only, and normal tissue without pathological changes was seen in group C. Of all 330 apoptosis-related genes analysed in human cell culture specimen, no significant difference was seen after pre-treatment with normal saline, compared with the gene chip without pre-treatment. On the gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and 34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted in the down-regulation of 3 apoptosis genes. Vitamin C can protect vascular endothelial cells from mannitol-induced injury.

  19. Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise.

    Science.gov (United States)

    Nishiyasu, Takeshi; Tsukamoto, Rina; Kawai, Katsuhito; Hayashi, Keiji; Koga, Shunsaku; Ichinose, Masashi

    2012-02-01

    Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P muscle regions.

  20. Role of α1D -adrenoceptors in vascular wall hypertrophy during angiotensin II-induced hypertension.

    Science.gov (United States)

    Gallardo-Ortíz, I A; Rodríguez-Hernández, S N; López-Guerrero, J J; Del Valle-Mondragón, L; López-Sánchez, P; Touyz, R M; Villalobos-Molina, R

    2015-09-01

    The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1 -adrenoceptors (α1 -ARs) expression was explored. Alzet(®) minipumps filled with Ang II (200 ng kg(-1)  min(-1) ) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1 R antagonist, or with BMY 7378, a selective α1D -AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses. Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups. Angiotensin II decreased α1D -ARs without modifying the other α1 -ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1 Rs and α1D -ARs. Angiotensin II-induced α1D -AR-mediated vascular remodeling occurs independently of hypertension. Findings identify a α1D -AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation. © 2016 John Wiley & Sons Ltd.

  1. PGC-1alpha inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Oleic acid (OA stimulates vascular smooth muscle cell (VSMC proliferation and migration. The precise mechanism is still unclear. We sought to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARgamma coactivator-1 alpha (PGC-1alpha on OA-induced VSMC proliferation and migration. PRINCIPAL FINDINGS: Oleate and palmitate, the most abundant monounsaturated fatty acid and saturated fatty acid in plasma, respectively, differently affect the mRNA and protein levels of PGC-1alpha in VSMCs. OA treatment resulted in a reduction of PGC-1alpha expression, which may be responsible for the increase in VSMC proliferation and migration caused by this fatty acid. In fact, overexpression of PGC-1alpha prevented OA-induced VSMC proliferation and migration while suppression of PGC-1alpha by siRNA enhanced the effects of OA. In contrast, palmitic acid (PA treatment led to opposite effects. This saturated fatty acid induced PGC-1alpha expression and prevented OA-induced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1alpha on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation. CONCLUSIONS: OA and PA regulate PGC-1alpha expression in VSMCs differentially. OA stimulates VSMC proliferation and migration via suppression of PGC-1alpha expression while PA reverses the effects of OA by inducing PGC-1alpha expression. Upregulation of PGC-1alpha in VSMCs provides a potential novel strategy in preventing atherosclerosis.

  2. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

    Directory of Open Access Journals (Sweden)

    Srabani Mitra

    Full Text Available Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1 induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  3. PDGF-BB and TGF-{beta}1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress.

    Science.gov (United States)

    Qi, Ying-Xin; Jiang, Jun; Jiang, Xiao-Hua; Wang, Xiao-Dong; Ji, Su-Ying; Han, Yue; Long, Ding-Kun; Shen, Bao-Rong; Yan, Zhi-Qiang; Chien, Shu; Jiang, Zong-Lai

    2011-02-01

    Shear stress, especially low shear stress (LowSS), plays an important role in vascular remodeling during atherosclerosis. Endothelial cells (ECs), which are directly exposed to shear stress, convert mechanical stimuli into intracellular signals and interact with the underlying vascular smooth muscle cells (VSMCs). The interactions between ECs and VSMCs modulate the LowSS-induced vascular remodeling. With the use of proteomic analysis, the protein profiles of rat aorta cultured under LowSS (5 dyn/cm(2)) and normal shear stress (15 dyn/cm(2)) were compared. By using Ingenuity Pathway Analysis to identify protein-protein association, a network was disclosed that involves two secretary molecules, PDGF-BB and TGF-β1, and three other linked proteins, lamin A, lysyl oxidase, and ERK 1/2. The roles of this network in cellular communication, migration, and proliferation were further studied in vitro by a cocultured parallel-plate flow chamber system. LowSS up-regulated migration and proliferation of ECs and VSMCs, increased productions of PDGF-BB and TGF-β1, enhanced expressions of lysyl oxidase and phospho-ERK1/2, and decreased Lamin A in ECs and VSMCs. These changes induced by LowSS were confirmed by using PDGF-BB recombinant protein, siRNA, and neutralizing antibody. TGF-β1 had similar influences on ECs as PDGF-BB, but not on VSMCs. Our results suggest that ECs convert the LowSS stimuli into up-regulations of PDGF-BB and TGF-β1, but these two factors play different roles in LowSS-induced vascular remodeling. PDGF-BB is involved in the paracrine control of VSMCs by ECs, whereas TGF-β1 participates in the feedback control from VSMCs to ECs.

  4. Evaluation of volume vascularization index and flow index: a phantom study.

    NARCIS (Netherlands)

    Schulten-Wijman, M.J.; Struijk, P.C.; Brezinka, C.; Jong, N De; Steegers, E.A.P.

    2008-01-01

    OBJECTIVES: Three-dimensional (3D) power Doppler ultrasonography provides indices to quantify moving blood within a volume of interest (e.g. ovary, endometrium, tumor or placenta). The purpose of this study was to determine the influence of ultrasound instrument settings on vascularization index (VI

  5. Flow structure and flow-induced noise in an axisymmetric cavity with lids

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seo Yoon [KAERI, Daejeon (Korea, Republic of); Sung, Hyung Jin [KAIST, Daejeon (Korea, Republic of)

    2016-07-15

    Direct numerical simulations of incompressible turbulent flow through an axisymmetric cavity with or without lids were performed at Re{sub t},{sub in} = 186 to examine the hydrodynamic effects of the lids on the flow-induced noise. The strength of the recirculation in the downstream region was weakened by the installation of the lids. Comparison of the acoustic sources of the Lighthill equation indicated that the lid in the downstream region attenuated the flow-induced noise substantially. Frequency spectra and spatio-temporal correlations of pressure fluctuations revealed the most energetic mode and the convective nature of the flow over the cavity. It was evident from a detailed investigation of the instantaneous flow fields that the introduction of lids into the cavity significantly weakened the interaction between the separated shear layer and the trailing edge of the cavity. The present results clearly showed that the installation of lids is an effective means of reducing flow-induced noise.

  6. Pituitary adenylate cyclase activating polypeptide induces vascular relaxation and inhibits non-vascular smooth muscle activity in the rabbit female genital tract

    DEFF Research Database (Denmark)

    Steenstrup, B R; Ottesen, B; Jørgensen, M

    1994-01-01

    a significant dose-related relaxation on the NA-precontracted vessels. However, pre-incubation of the vessels with 10(-7) M PACAP-38, PACAP-27 and vaso active intestinal polypeptide (VIP) did not induce a general rightward shift of the NA concentration-response curves, although a tendency to inhibition......In vitro effects of two bioactive forms of pituitary adenylate cyclase activating polypeptide (PACAP): PACAP-38 and PACAP-27 were studied on rabbit vascular and non-vascular smooth muscle. Segments of the ovarian artery and muscle strips from the fallopian tube were used. Two series of experiments...... in the low-dose interval was observed. The peptides caused a significant, dose-dependent inhibition of both frequency and amplitude on the fallopian tube smooth muscle activity. The effects of the three peptides on longitudinally as well as transversally cut specimens were alike....

  7. Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats.

    Science.gov (United States)

    Minutoli, Letteria; Arena, Salvatore; Bonvissuto, Giulio; Bitto, Alessandra; Polito, Francesca; Irrera, Natasha; Arena, Francesco; Fragalà, Eugenia; Romeo, Carmelo; Nicotina, Piero Antonio; Fazzari, Carmine; Marini, Herbert; Implatini, Alessandra; Grimaldi, Silvia; Cantone, Noemi; Di Benedetto, Vincenzo; Squadrito, Francesco; Altavilla, Domenica; Morgia, Giuseppe

    2011-03-15

    In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele.

  8. Effect of the two new calcium channel blockers mebudipine and dibudipine in comparison to amlodipine on vascular flow of isolated kidney of diabetic rat.

    Science.gov (United States)

    Sepehr-Ara, L; Sepehr-Ara, M; Mahmoudian, M

    2010-09-01

    Calcium channel blockers are clinically useful vasodilators, used widely in the treatment of hypertension. These agents are reported to preserve or improve renal function in patients with essential hypertensive renal disease or diabetic renal disease. Among the classes of calcium channel blockers, dihydropyridine derivatives are widely used because of their potent vasodilating activity and weak cardiodepressant action. Mebudipine and dibudipine are two new 1,4-dihydropyridine calcium channel blockers that recently have been synthesized. In previous research mebudipine and dibudipine showed considerable relaxant effects on vascular and ileal smooth muscle cells. In this study we investigated the effects of these new drugs on vascular flow of isolated kidney of diabetic rat and compare their potencies to amlodipine. It is concluded that mebudipine and dibudipine (1-10 μM) are at least as potent as amlodipine in inhibiting PE-induced perfusion pressure in isolated kidney of diabetic rats. These new dihydropyridines improve kidney perfusion of diabetic rat in the setting of PE infusion. Similarly, amlodipine.

  9. Thigh muscle size and vascular function after blood flow-restricted elastic band training in older women

    Science.gov (United States)

    Yasuda, Tomohiro; Fukumura, Kazuya; Tomaru, Takanobu; Nakajima, Toshiaki

    2016-01-01

    We examined the effect of elastic band training with blood flow restriction (BFR) on thigh muscle size and vascular function in older women. Older women were divided into three groups: low-intensity elastic band BFR training (BFR-Tr, n = 10), middleto high-intensity elastic band training (MH-Tr, n = 10), and no training (Ctrl, n = 10) groups. BFR-Tr and MH-Tr groups performed squat and knee extension exercises using elastic band, 2 days/week for 12 weeks. During BFR-Tr exercise session, subjects wore pressure cuffs around the most proximal region of both thighs. The following measurements were taken before (pre) and 3-5 days after (post) the final training session: MRI-measured muscle cross-sectional area (CSA) at mid-thigh, maximum voluntary isometric contraction (MVIC) of knee extension, central systolic blood pressure (c-SBP), central-augmentation index (c-AIx), cardio-ankle vascular index testing (CAVI), ankle-brachial pressure index (ABI). Quadriceps muscle CSA (6.9%) and knee extension MVIC (13.7%) were increased (p muscle CSA as well as maximal muscle strength, but does not decrease vascular function in older women. PMID:27244884

  10. Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

    Directory of Open Access Journals (Sweden)

    Melemedjian Ohannes K

    2008-03-01

    Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

  11. Flow induced pulsations in pipe systems

    Science.gov (United States)

    Bruggeman, Jan Cornelis

    1987-12-01

    The aeroacoustic behavior of a low Mach number, high Reynolds number flow through a pipe with closed side branches was investigated. Sound is generated by coherent structures of concentrated vorticity formed periodically in the separated flow in the T-shaped junctions of side branches and the main pipe. The case of moderate pulsation amplitudes was investigated. It appears that the vortical flow in a T-joint is an aeroacoustic source of constant strength when acoustic energy losses due to radiation and friction are small but not negligible. When acoustic energy losses due to radiation and friction are negligible, the nonlinear character of vortex damping is the amplitude limiting mechanism. It is stressed that aeroacoustic sources should not be neglected in studies of the response of a piping lay-out with flow to, e.g., the pulsating output of a compressor.

  12. Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction.

    Science.gov (United States)

    Balasubramanian, Lavanya; Lo, Chun-Min; Sham, James S K; Yip, Kay-Pong

    2013-02-15

    It was previously demonstrated in isolated renal vascular smooth muscle cells (VSMCs) that integrin-mediated mechanotransduction triggers intracellular Ca(2+) mobilization, which is the hallmark of myogenic response in VSMCs. To test directly whether integrin-mediated mechanotransduction results in the myogenic response-like behavior in renal VSMCs, cell traction force microscopy was used to monitor cell traction force when the cells were pulled with fibronectin-coated or low density lipoprotein (LDL)-coated paramagnetic beads. LDL-coated beads were used as a control for nonintegrin-mediated mechanotransduction. Pulling with LDL-coated beads increased the cell traction force by 61 ± 12% (9 cells), which returned to the prepull level after the pulling process was terminated. Pulling with noncoated beads had a minimal increase in the cell traction force (12 ± 9%, 8 cells). Pulling with fibronectin-coated beads increased the cell traction force by 56 ± 20% (7 cells). However, the cell traction force was still elevated by 23 ± 14% after the pulling process was terminated. This behavior is analogous to the changes of vascular resistance in pressure-induced myogenic response, in which vascular resistance remains elevated after myogenic constriction. Fibronectin is a native ligand for α(5)β(1)-integrins in VSMCs. Similar remanent cell traction force was found when cells were pulled with beads coated with β(1)-integrin antibody (Ha2/5). Activation of β(1)-integrin with soluble antibody also triggered variations of cell traction force and Ca(2+) mobilization, which were abolished by the Src inhibitor. In conclusion, mechanical force transduced by α(5)β(1)-integrins triggered a myogenic response-like behavior in isolated renal VSMCs.

  13. Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties.

    Directory of Open Access Journals (Sweden)

    Priscila Portugal Dos Santos

    Full Text Available The aim of this study was to evaluate whether supplementation of high doses of cholecalciferol for two months in normotensive rats results in increased systolic arterial pressure and which are the mechanisms involved. Specifically, this study assesses the potential effect on cardiac output as well as the changes in aortic structure and functional properties.Male Wistar rats were divided into three groups: 1 Control group (C, n = 20, with no supplementation of vitamin D, 2 VD3 (n = 19, supplemented with 3,000 IU vitamin D/kg of chow; 3 VD10 (n = 21, supplemented with 10,000 IU vitamin D/kg of chow. After two months, echocardiographic analyses, measurements of systolic arterial pressure (SAP, vascular reactivity, reactive oxygen species (ROS generation, mechanical properties, histological analysis and metalloproteinase-2 and -9 activity were performed.SAP was higher in VD3 and VD10 than in C rats (p = 0.001. Echocardiographic variables were not different among groups. Responses to phenylephrine in endothelium-denuded aortas was higher in VD3 compared to the C group (p = 0.041. Vascular relaxation induced by acetylcholine (p = 0.023 and sodium nitroprusside (p = 0.005 was impaired in both supplemented groups compared to the C group and apocynin treatment reversed impaired vasodilation. Collagen volume fraction (<0.001 and MMP-2 activity (p = 0.025 was higher in VD10 group compared to the VD3 group. Elastin volume fraction was lower in VD10 than in C and yield point was lower in VD3 than in C.Our findings support the view that vitamin D supplementation increases arterial pressure in normotensive rats and this is associated with structural and functional vascular changes, modulated by NADPH oxidase, nitric oxide, and extracellular matrix components.

  14. Effect of Oxysterol-Induced Apoptosis of Vascular Smooth Muscle Cells on Experimental Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Sonia Perales

    2009-01-01

    Full Text Available Smooth muscle cells (SMCs undergo changes related to proliferation and apoptosis in the physiological remodeling of vessels and in diseases such as atherosclerosis and restenosis. Recent studies also have demonstrated the vascular cell proliferation and programmed cell death contribute to changes in vascular architecture in normal development and in disease. The present study was designed to investigate the apoptotic pathways induced by 25-hydroxycholesterol in SMCs cultures, using an in vivo/in vitro cell model in which SMCs were isolated and culture from chicken exposed to an atherogenic cholesterol-rich diet (SMC-Ch and/or an antiatherogenic fish oil-rich diet (SMC-Ch-FO. Cells were exposed in vitro to 25-hydroxycholesterol to study levels of apoptosis and apoptotic proteins Bcl-2, Bcl-XL and Bax and the expression of bcl-2 and bcl-xL, genes. The quantitative real-time reverse transcriptase-polymerase chain reaction and the Immunoblotting western blot analysis showed that 25-hydroxycholesterol produces apoptosis in SMCs, mediated by a high increase in Bax protein and Bax gene expression. These changes were more marked in SMC-Ch than in SMC-Ch-FO, indicating that dietary cholesterol produces changes in SMCs that make them more susceptible to 25-hydroxycholesterol-mediated apoptosis. Our results suggest that the replacement of a cholesterol-rich diet with a fish oil-rich diet produces some reversal of cholesterol-induced changes in the apoptotic pathways induced by 25-hydroxycholesterol in SMCs cultures, making SMCs more resistant to apoptosis.

  15. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats.

    Science.gov (United States)

    Babacanoglu, C; Yildirim, N; Sadi, G; Pektas, M B; Akar, F

    2013-10-01

    Dietary intake of fructose and sucrose can cause development of metabolic and cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a commonly consumed form of fructose and glucose, have poorly been examined. Therefore, in this study, we investigated whether HFCS intake (10% and 20% beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1 in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats. At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights of rats. Impaired nitric oxide-mediated relaxation to insulin (10⁻⁹ to 3×10⁻⁶ M), and enhanced contraction to endothelin-1 (10⁻¹¹ to 10⁻⁸ M) were associated with decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS production. In conclusion, dietary HFCS causes vascular insulin resistance and endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced disturbances.

  16. Sinusoidal Constriction and Vascular Hypertrophy in the Diabetes-Induced Rabbit Penis

    Directory of Open Access Journals (Sweden)

    Vivian Alves Pereira

    2013-06-01

    Full Text Available Objective To assess the morphological changes of penile vascular structures and the corpus cavernosum area in alloxan-induced diabetic rabbits. Materials and Methods Twenty male rabbits (2 months old were divided into two groups with 10 rabbits each, the control group (CG and the diabetic group (DG. The animals from DG received an intravenous injection of alloxan (100mg/kg to induce the diabetes. Ten weeks after the induction of diabetes, all animals were euthanized. Two fragments of the penile shaft were harvested and samples were processed and paraffin embedded. Sections (5µm were cut and stained for histological and immunohistochemical markers. Results Nuclear protrusion toward the lumen, and cytoplasmic vacuolization were observed in the tunica intima of the dorsal artery of the penis in DG. The thicknesses of the tunica media increased significantly in DG (p = 0.0350. It was also observed a significant increase in the area of the tunica media (p = 0.0179. There was no significant change in smooth muscle cell density in the tunica media of the dorsal artery of the penis (p = 0.0855. The collagen fiber pattern of the tunica adventitia of the dorsal artery of the penis was different between the control and diabetic groups. There was a significant decrease in the area occupied by the cavernous sinuses in DG (p = 0.0013. Conclusion Alloxan-induced diabetes mellitus in rabbits promotes important changes in penile vascular structures, thereby decreasing blood supply and affecting penile hemodynamics, leading to erectile dysfunction.

  17. Flow Induced segregation in full scale castings with SCC

    DEFF Research Database (Denmark)

    Thrane, Lars Nyholm; Stang, Henrik; Geiker, Mette Rica

    2007-01-01

    Though promising, pioneering work has been carried out with rheological characterization and numerical modelling of form filling with SCC, the approach is far from standard in the concrete industry and clearly the approach does not yet hold all the answers to relevant questions. In particular flow...... induced segregation is a major risk during casting and it is not yet clear how this phenomenon should be modelled. In this paper testing and numerical simulations of full-scale wall castings are compared. Two different SCCs and three different filling methods were applied resulting in different flow...... patterns during form filling. Results show that the flow patterns have a major influence on the risk of flow induced segregation and the surface finish of the hardened concrete. A hypothesis for the mechanism of flow induced segregation is put forth....

  18. Coronal Jet Collimation by Nonlinear Induced Flows

    Science.gov (United States)

    Vasheghani Farahani, S.; Hejazi, S. M.

    2017-08-01

    Our objective is to study the collimation of solar jets by nonlinear forces corresponding to torsional Alfvén waves together with external forces. We consider a straight, initially non-rotating, untwisted magnetic cylinder embedded in a plasma with a straight magnetic field, where a shear between the internal and external flows exists. By implementing magnetohydrodynamic theory and taking into account the second-order thin flux tube approximation, the balance between the internal nonlinear forces is visualized. The nonlinear differential equation containing the ponderomotive, magnetic tension, and centrifugal forces in the presence of the shear flow is obtained. The solution presents the scale of influence of the propagating torsional Alfvén wave on compressive perturbations. Explicit expressions for the compressive perturbations caused by the forces connected to the torsional Alfvén wave show that, in the presence of a shear flow, the magnetic tension and centrifugal forces do not cancel each other’s effects as they did in its absence. This shear flow plays in favor of the magnetic tension force, resulting in a more efficient collimation. Regarding the ponderomotive force, the shear flow has no effect. The phase relations highlight the interplay of the shear flow and the plasma-β. As the shear flow and plasma-β increase, compressive perturbation amplitudes emerge. We conclude that the jet collimation due to the torsional Alfvén wave highly depends on the location of the jet. The shear flow tightens the collimation as the jet elevates up to the solar corona.

  19. Inertially-induced secondary flow in microchannels

    CERN Document Server

    Amini, Hamed; Di Carlo, Dino

    2011-01-01

    We report a novel technique to passively create strong secondary flows at moderate to high flow rates in microchannels, accurately control them and finally, due to their deterministic nature, program them into microfluidic platforms. Based on the flow conditions and due to the presence of the pillars in the channel, the flow streamlines will lose their fore-aft symmetry. As a result of this broken symmetry the fluid is pushed away from the pillar at the center of the channel (i.e. central z-plane). As the flow needs to maintain conservation of mass, the fluid will laterally travel in the opposite direction near the top and bottom walls. Therefore, a NET secondary flow will be created in the channel cross-section which is depicted in this video. The main platform is a simple straight channel with posts (i.e. cylindrical pillars - although other pillar cross-sections should also function) placed along the channel. Channel measures were 200 \\mum\\times50 \\mum, with pillars of 100 \\mum in diameter. Positioning the...

  20. Unconjugated bilirubin mediates heme oxygenase-1-induced vascular benefits in diabetic mice.

    Science.gov (United States)

    Liu, Jian; Wang, Li; Tian, Xiao Yu; Liu, Limei; Wong, Wing Tak; Zhang, Yang; Han, Quan-Bin; Ho, Hing-Man; Wang, Nanping; Wong, Siu Ling; Chen, Zhen-Yu; Yu, Jun; Ng, Chi-Fai; Yao, Xiaoqiang; Huang, Yu

    2015-05-01

    Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose-induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy.

  1. Turbulence measurements in shock induced flow using hot wire anemometry

    Science.gov (United States)

    Hartung, Lin C.; Duffy, Robert E.; Trolier, James W.

    1988-01-01

    Heat transfer measurements over various geometric shapes have been made by immersing models in shock-induced flows. The heat transfer to a body is strongly dependent on the turbulence level of the stream. The interpretation of such heat transfer measurements requires a knowledge of the turbulence intensity. Turbulence intensity measurements, using hot-wire anemometry, have been successfully carried out in shock-induced flows. The experimental procedures for making such measurements and the techniques required are discussed.

  2. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    Science.gov (United States)

    Rouver, Wender Nascimento; Delgado, Nathalie Tristão Banhos; Menezes, Jussara Bezerra; Santos, Roger Lyrio; Moyses, Margareth Ribeiro

    2015-01-01

    The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

  3. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    Directory of Open Access Journals (Sweden)

    Wender Nascimento Rouver

    Full Text Available The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM, castrated (CAST, castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group or supraphysiological dose (2.5 mg/kg/day, SUPRA group of testosterone for 15 days. Systolic blood pressure (SBP was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO, L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT. We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

  4. Cytokine-Induced Cell Surface Expression of Adhesion Molecules in Vascular Endothelial Cells In vitro

    Institute of Scientific and Technical Information of China (English)

    陈红辉; 刘昌勤; 孙圣刚; 梅元武; 童萼塘

    2001-01-01

    Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF-α (1-250 U/ml) or IL-1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-α (100 U/ml) or IL-1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up-regulated by TNF-α, IL-1β in a concentration- and time-dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.

  5. Flow-induced vibration of circular cylindrical structures

    Energy Technology Data Exchange (ETDEWEB)

    Chen, S.S.

    1985-06-01

    This report summarizes the flow-induced vibration of circular cylinders in quiescent fluid, axial flow, and crossflow, and applications of the analytical methods and experimental data in design evaluation of various system components consisting of circular cylinders. 219 figs., 30 tabs. (JDB)

  6. Subcutaneous blood flow during insulin-induced hypoglycaemia

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Sestoft, L

    1982-01-01

    Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms...

  7. Endometrial vascularity is lower in pregnancies with pregnancy-induced hypertension or small-for-gestational-age fetus in live birth after in-vitro fertilization.

    Science.gov (United States)

    Lai, C W S; Yung, S S F; Ng, E H Y

    2014-10-01

    To assess the relationship between endometrial/subendometrial vascularity and the risk of pregnancy-induced hypertension (PIH) or small-for-gestational-age (SGA) fetuses in women who had a live birth following in-vitro fertilization (IVF). This was a retrospective study of women who had a live birth after IVF from November 2002 to December 2004. Only women with a singleton pregnancy (n = 104) were included for analysis. Three-dimensional ultrasound measurement with power Doppler of the endometrial and subendometrial regions was performed on the day of oocyte retrieval in stimulated IVF cycles or on luteinizing hormone surge + 1 day in frozen-thawed embryo transfer cycles to measure the endometrial volume and the vascularization index (VI), flow index (FI) and vascularization flow index (VFI) of the endometrial and subendometrial regions. Pregnancy outcomes were also reviewed. Eight women (7.7%) had PIH or an SGA fetus. Women in the PIH/SGA group had significantly lower endometrial VI (0.504 vs 1.051; P = 0.023) and VFI (0.121 vs 0.253; P = 0.023) than those in the non-PIH/SGA group. However endometrial FI was significantly higher in the PIH/SGA group (23.04 vs 22.71; P = 0.028). There were no significant differences in subendometrial indices between the two groups. Women who had a live birth following IVF and whose pregnancy was complicated by PIH or an SGA fetus had significantly lower endometrial vascularity in terms of VI and VFI than did women without PIH or SGA. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  8. In vitro stimulation of vascular endothelial growth factor by borate-based glass fibers under dynamic flow conditions.

    Science.gov (United States)

    Chen, Sisi; Yang, Qingbo; Brow, Richard K; Liu, Kun; Brow, Katherine A; Ma, Yinfa; Shi, Honglan

    2017-04-01

    Bioactive borate glass has been recognized to have both hard and soft tissue repair and regeneration capabilities through stimulating both osteogenesis and angiogenesis. However, the underlying biochemical and cellular mechanisms remain unclear. In this study, dynamic flow culturing modules were designed to simulate the micro-environment near the vascular depletion and hyperplasia area in wound-healing regions, thus to better investigate the mechanisms underlying the biocompatibility and functionality of borate-based glass materials. Glass fibers were dosed either upstream or in contact with the pre-seeded cells in the dynamic flow module. Two types of borate glasses, doped with (1605) or without (13-93B3) CuO and ZnO, were studied along with the silicate-based glass, 45S5. Substantial fiber dissolution in cell culture medium was observed, leading to the release of ions (boron, sodium and potassium) and the deposition of a calcium phosphate phase. Different levels of vascular endothelial growth factor secretion were observed from cells exposed to these three glass fibers, and the copper/zinc containing borate 1605 fibers exhibited the most positive influence. These results indicate that dynamic studies of in vitro bioactivity provide useful information to understand the in vivo response to bioactive borate glasses. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Brown fat lipoatrophy and increased visceral adiposity through a concerted adipocytokines overexpression induces vascular insulin resistance and dysfunction.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Otero, Yolanda F; de las Heras, Natalia; Escribano, Oscar; Cachofeiro, Victoria; Lahera, Vicente; Benito, Manuel

    2012-03-01

    In this study, we analyzed the role played by concerted expression of adipocytokines associated with brown fat lipoatrophy and increased visceral adiposity on triggering vascular insulin resistance and dysfunction in brown adipose tissue (BAT) insulin receptor knockout (BATIRKO) mice. In addition, we assessed whether vascular insulin resistance may aggravate vascular damage. The 52-wk-old, but not 33-wk-old, BATIRKO mice had a significant decrease of BAT mass associated with a significant increase of visceral white adipose tissue (WAT) mass, without changes in body weight. Brown fat lipoatrophy and increased visceral adiposity enhanced the concerted expression of adipocytokines (TNF-α, leptin, and plasminogen activator inhibitor 1) and nuclear factor-κB binding activity in BAT and visceral WAT, mainly in the gonadal depot, and aorta. Although those mice showed insulin sensitivity in the liver and skeletal muscle, insulin signaling in WAT (gonadal depot) and aorta was markedly impaired. Treatment with anti-TNF-α antibody impaired the inflammatory activity in visceral adipose tissue, attenuated insulin resistance in WAT and aorta and induced glucose tolerance. Finally, 52-wk-old BATIRKO mice showed vascular dysfunction, macrophage infiltration, oxidative stress, and a significant increase of gene markers of endothelial activation and inflammation, the latter effect being totally reverted by anti-TNF-α antibody treatment. Our results suggest that brown fat lipoatrophy and increased visceral adiposity through the concerted overexpression of cytoadipokines induces nuclear factor-κB-mediated inflammatory signaling, vascular insulin resistance, and vascular dysfunction. Inhibition of inflammatory activity by anti-TNF-α antibody treatment attenuates vascular insulin resistance and impairs gene expression of vascular dysfunction markers.

  10. Effects of intracellular alkalinization on resting and agonist-induced vascular tone.

    Science.gov (United States)

    Danthuluri, N R; Deth, R C

    1989-03-01

    To evaluate the influence of intracellular alkalinization on basal and agonist-induced vascular tone, we studied the effect of NH4Cl on rat aorta. NH4Cl induced a gradually developing contraction in a dose-dependent manner. Although the contractile response to 20 mM NH4Cl was associated with a latent period (LP) of 23.4 +/- 2.8 min, intracellular pH (pHi) measurements in cultured rat aortic smooth muscle cells showed that NH4Cl-induced intracellular alkalinization was immediate and transient, returning to basal pHi levels in about 30-35 min. Agents that elevate Ca2+, such as A23187 and high KCl, significantly reduced the LP associated with 20 mM NH4Cl-induced contraction. NH4Cl-induced contractions were sensitive to extracellular Ca2+ removal and to the addition of forskolin (1 microM); however, NH4Cl by itself did not cause Ca2+-influx as shown by 45Ca-uptake studies. Addition of 20 mM NH4Cl to precontracted tissues resulted in a transient relaxation, which was complete in approximately 10 min, followed by a contraction above the original level of tone. NH4Cl pretreatment caused time-dependent alterations in both the rapid and slow phases of phenylephrine and angiotensin II contractions. Rapid-phase of phenylephrine and angiotensin II contractions. Rapid-phase responses were diminished at shorter NH4Cl incubation times (10 min), whereas slow-phase response was augmented after a longer incubation (20 min). Overall, the vasorelaxant and vasoconstrictor effects induced by NH4Cl suggest a complex relationship between intracellular alkalinization and arterial contractility.

  11. The novel role of fenofibrate in preventing nicotine- and sodium arsenite-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Kaur, Jagdeep; Reddy, Krishna; Balakumar, Pitchai

    2010-09-01

    The present study investigated the effect of fenofibrate, an agonist of PPAR-alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning electron microscopy study in thoracic aorta revealed that administration of nicotine or sodium arsenite impaired the integrity of vascular endothelium. Further, administration of nicotine or sodium arsenite significantly decreased serum and aortic concentrations of nitrite/nitrate and subsequently reduced acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide generation. However, treatment with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a standard agent) significantly prevented nicotine- and sodium arsenite-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Conversely, co-administration of L-NAME (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated these vascular protective effects of fenofibrate. The administration of nicotine or sodium arsenite altered the lipid profile by increasing serum cholesterol and triglycerides and consequently decreasing high-density lipoprotein levels, which were significantly prevented by treatment with fenofibrate or atorvastatin. It may be concluded that fenofibrate improves the integrity and function of vascular endothelium, and the vascular protecting potential of fenofibrate in preventing the development of nicotine- and sodium arsenite-induced VED may be attributed to its

  12. G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension.

    Science.gov (United States)

    Wirth, Angela; Benyó, Zoltán; Lukasova, Martina; Leutgeb, Barbara; Wettschureck, Nina; Gorbey, Stefan; Orsy, Petra; Horváth, Béla; Maser-Gluth, Christiane; Greiner, Erich; Lemmer, Björn; Schütz, Günther; Gutkind, J Silvio; Offermanns, Stefan

    2008-01-01

    The tone of vascular smooth muscle cells is a primary determinant of the total peripheral vascular resistance and hence the arterial blood pressure. Most forms of hypertension ultimately result from an increased vascular tone that leads to an elevated total peripheral resistance. Regulation of vascular resistance under normotensive and hypertensive conditions involves multiple mediators, many of which act through G protein-coupled receptors on vascular smooth muscle cells. Receptors that mediate vasoconstriction couple with the G-proteins G(q)-G11 and G12-G13 to stimulate phosphorylation of myosin light chain (MLC) via the Ca2+/MLC kinase- and Rho/Rho kinase-mediated signaling pathways, respectively. Using genetically altered mouse models that allow for the acute abrogation of both signaling pathways by inducible Cre/loxP-mediated mutagenesis in smooth muscle cells, we show that G(q)-G11-mediated signaling in smooth muscle cells is required for maintenance of basal blood pressure and for the development of salt-induced hypertension. In contrast, lack of G12-G13, as well as of their major effector, the leukemia-associated Rho guanine nucleotide exchange factor (LARG), did not alter normal blood pressure regulation but did block the development of salt-induced hypertension. This identifies the G12-G13-LARG-mediated signaling pathway as a new target for antihypertensive therapies that would be expected to leave normal blood pressure regulation unaffected.

  13. Vascular disease modeling using induced pluripotent stem cells: Focus in Hutchinson-Gilford Progeria Syndrome.

    Science.gov (United States)

    Pitrez, P R; Rosa, S C; Praça, C; Ferreira, L

    2016-05-06

    Induced pluripotent stem cells (iPSCs) represent today an invaluable tool to create disease cell models for modeling and drug screening. Several lines of iPSCs have been generated in the last 7 years that changed the paradigm for studying diseases and the discovery of new drugs to treat them. In this article we focus our attention to vascular diseases in particular Hutchinson-Gilford Progeria Syndrome (HGPS), a devastating premature aging disease caused by a mutation in the lamin A gene. In general, patients die because of myocardial infarction or stroke. Because the patients are fragile the isolation of a particular type of cells is very difficult. Therefore in the last 5 years, researchers have used cells derived from iPSCs to model aspects of the HGPS and to screen libraries of chemicals to retard or treat the disease.

  14. A novel concept of measuring mass flow rates using flow induced stresses

    Indian Academy of Sciences (India)

    P I Jagad; B P Puranik; A W Date

    2015-08-01

    Measurement of mass flow rate is important for automatic control of the mass flow rate in many industries such as semiconductor manufacturing and chemical industry (for supply of catalyst to a reaction). In the present work, a new concept for direct measurement of mass flow rates which does not depend on the volumetric flow rate measurement and obviates the need for the knowledge of density is proposed from the measurement of the flow induced stresses in a substrate. The concept is formulated by establishing the relationship between the mass flow rate and the stress in the substrate. To this end, the flow field and the stress field in the substrate are evaluated simultaneously using a numerical procedure and the necessary correlations are derived. A least squares based procedure is used to derive the mass flow rate from the correlations as a function of the stress in the substrate.

  15. Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

    Directory of Open Access Journals (Sweden)

    Ho Sub Lee

    2012-01-01

    Full Text Available Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV on high glucose (HG-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS. HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1, eNOS, and nuclear factor E2-related factor 2 (Nrf2, which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.

  16. Modeling of [Formula: see text]-mediated calcium signaling in vascular endothelial cells induced by fluid shear stress and ATP.

    Science.gov (United States)

    Li, Long-Fei; Xiang, Cheng; Qin, Kai-Rong

    2015-10-01

    The calcium signaling plays a vital role in flow-dependent vascular endothelial cell (VEC) physiology. Variations in fluid shear stress and ATP concentration in blood vessels can activate dynamic responses of cytosolic-free [Formula: see text] through various calcium channels on the plasma membrane. In this paper, a novel dynamic model has been proposed for transient receptor potential vanilloid 4 [Formula: see text]-mediated intracellular calcium dynamics in VECs induced by fluid shear stress and ATP. Our model includes [Formula: see text] signaling pathways through P2Y receptors and [Formula: see text] channels (indirect mechanism) and captures the roles of the [Formula: see text] compound channels in VEC [Formula: see text] signaling in response to fluid shear stress (direct mechanism). In particular, it takes into account that the [Formula: see text] compound channels are regulated by intracellular [Formula: see text] and [Formula: see text] concentrations. The simulation studies have demonstrated that the dynamic responses of calcium concentration produced by the proposed model correlate well with the existing experimental observations. We also conclude from the simulation studies that endogenously released ATP may play an insignificant role in the process of intracellular [Formula: see text] response to shear stress.

  17. ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

    Science.gov (United States)

    Huang, Xu; Xu, Meng-Qi; Zhang, Wei; Ma, Sai; Guo, Weisheng; Wang, Yabin; Zhang, Yan; Gou, Tiantian; Chen, Yundai; Liang, Xing-Jie; Cao, Feng

    2017-05-01

    The proliferation of vascular smooth muscle cells (VSMCs) is one of the key events during the progress of atherosclerosis. The activated liver X receptor (LXR) signalling pathway is demonstrated to inhibit platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation. Notably, following PDGF-BB stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by VSMCs increases significantly. In this study, anti-ICAM-1 antibody-conjugated liposomes were fabricated for targeted delivery of a water-insoluble LXR agonist (T0901317) to inhibit VSMC proliferation. The liposomes were prepared by filming-rehydration method with uniform size distribution and considerable drug entrapment efficiency. The targeting effect of the anti-ICAM-T0901317 liposomes was evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Anti-ICAM-T0901317 liposomes showed significantly higher inhibition effect of VSMC proliferation than free T0901317 by CCk8 proliferation assays and BrdU staining. Western blot assay further confirmed that anti-ICAM-T0901317 liposomes inhibited retinoblastoma (Rb) phosphorylation and MCM6 expression. In conclusion, this study identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression.

  18. Blood flow and vascular reactivity during attacks of classic migraine--limitations of the Xe-133 intraarterial technique

    Energy Technology Data Exchange (ETDEWEB)

    Skyhoj Olsen, T.; Lassen, N.A.

    1989-01-01

    The present study reports cerebral blood flow (CBF) measurements in 11 patients during attacks of classic migraine (CM)--migraine with aura. In 6 and 7 patients, respectively, cerebral vascular reactivity to increased blood pressure and to hypocapnia was also investigated during the CM attacks. The Xenon-133 intraarterial injection technique was used to measure CBF. In this study, based in part on previously published data, methodological limitations, in particular caused by scattered radiation (Compton scatter), are critically analysed. Based on this analysis and the results of the CBF studies it is concluded: During CM attacks CBF appears to decrease focally in the posterior part of the brain to a level around 20 ml/100 g/min which is consistent with a mild degree of ischemia. Changes of CBF in focal low flow areas are difficult to evaluate accurately with the Xe-133 technique. In most cases true CBF may change 50% or more in the low flow areas without giving rise to significantly measurable changes of CBF. This analysis suggests that the autoregulation response cannot be evaluated in the low flow areas with the technique used while the observations are compatible with the concept that a vasoconstrictive state, unresponsive to hypocapnia, prevails in the low flow areas during CM attacks. The gradual increase in size of the low flow area seen in several cases may be interpreted in two different ways. A spreading process may actually exist. However, due to Compton scatter, a gradual decrease of CBF in a territory that does not increase in size will also appear as a gradually spreading low flow area when studied with the Xe-133 intracarotid technique.

  19. ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration.

    Science.gov (United States)

    Hortelano, Sonsoles; López-Fontal, Raquel; Través, Paqui G; Villa, Natividad; Grashoff, Carsten; Boscá, Lisardo; Luque, Alfonso

    2010-05-01

    The inflammatory response to injurious agents is tightly regulated to avoid adverse consequences of inappropriate leucocyte accumulation or failed resolution. Lipopolysaccharide (LPS)-activated endothelium recruits leucocytes to the inflamed tissue through controlled expression of membrane-associated adhesion molecules. LPS responses in macrophages are known to be regulated by integrin-linked kinase (ILK); in this study, we investigated the role of ILK in the regulation of the LPS-elicited inflammatory response in endothelium. This study was performed on immortalized mouse endothelial cells (EC) isolated from lung and coronary vasculature. Cells were thoroughly characterized and the role of ILK in the regulation of the LPS response was investigated by suppressing ILK expression using siRNA and shRNA technologies. Phenotypic and functional analyses confirmed that the immortalized cells behaved as true EC. LPS induced the expression of the inflammatory genes E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). ILK knockdown impaired LPS-mediated endothelial activation by preventing the induction of ICAM-1 and VCAM-1. Blockade of the LPS-induced response inhibited the inflammatory-related processes of firm adhesion and trans-endothelial migration of leucocytes. ILK is involved in the expression of cell adhesion molecules by EC activated with the inflammatory stimulus LPS. This reduced expression modulates leucocyte adhesion to the endothelium and the extravasation process. This finding suggests ILK as a potential anti-inflammatory target for the development of vascular-specific treatments for inflammation-related diseases.

  20. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Connie Slocum

    2014-07-01

    Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

  1. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

    Science.gov (United States)

    Slocum, Connie; Coats, Stephen R; Hua, Ning; Kramer, Carolyn; Papadopoulos, George; Weinberg, Ellen O; Gudino, Cynthia V; Hamilton, James A; Darveau, Richard P; Genco, Caroline A

    2014-07-01

    Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS) structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4) agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/-) mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/-) mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune detection at TLR4

  2. Inhibitive effects of anti-oxidative vitamins on mannitol-induced apoptosis of vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    PAN Kai-yu; SHEN Mei-ping; YE Zhi-hong; DAI Xiao-na; SHANG Shi-qiang

    2006-01-01

    Objective: Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Methods: Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was performed with normal saline (group B), vitamin C (group C) and vitamin E (group D). Blood vessel injury was assessed under electron and light microscopy. In a second experiment, cell culture specimen of human umbilical vein endothelial cells were treated with mannitol. Pre-treatment was done with normal saline (sample B), vitamin C (sample C) and vitamin E (sample D).Total RNA was extracted with the original single step procedure, followed by hybridisation and analysis of gene expression.Results: In the animal experiment, serious blood vessel injury was seen in group A and group B. Group D showed light injury only,and normal tissue without pathological changes was seen in group C. Of all 330 apoptosis-related genes analysed in human cell culture specimen, no significant difference was seen after pre-treatment with normal saline, compared with the gene chip without pre-treatment. On the gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and 34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted in the down-regulation of 3 apoptosis genes. Conclusion: Vitamin C can protect vascular endothelial cells from mannitol-induced injury.

  3. In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation.

    Science.gov (United States)

    Martínez-Moreno, Julio M; Muñoz-Castañeda, Juan R; Herencia, Carmen; Oca, Addy Montes de; Estepa, Jose C; Canalejo, Rocio; Rodríguez-Ortiz, Maria E; Perez-Martinez, Pablo; Aguilera-Tejero, Escolástico; Canalejo, Antonio; Rodríguez, Mariano; Almadén, Yolanda

    2012-10-15

    The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10(-8)M (HP + CTR) or paricalcitol 3·10(-8) M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways.

  4. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  5. A novel mouse model of high flow-induced pulmonary hypertension-surgically induced by right pulmonary artery ligation.

    Science.gov (United States)

    Zhang, Anchen; Wang, Hongfei; Wang, Shengwei; Huang, Xiaofan; Ye, Ping; Du, Xinling; Xia, Jiahong

    2017-02-01

    This study sought to establish a new model of high-flow pulmonary hypertension (PH) in mice. This model may be useful for studies seeking to reduce the pulmonary vascular resistance and delay the development of PH caused by congenital heart disease. The right pulmonary artery was ligated via a right posterolateral thoracotomy. Pulmonary hemodynamics was evaluated by right heart catheterization immediately after ligation and at 2, 4, 8, and 12 wk postoperatively. The right ventricle (RV) and the left ventricle (LV) with septum (S) were weighed to calculate the RV/(LV + S) ratio as an index of right ventricular hypertrophy. Morphologic changes in the left lungs were analyzed, and percentages of muscularized pulmonary vessels were assessed by hematoxylin and eosin, elastica van Gieson and alpha-smooth muscle actin staining. All the study data were compared with data from a model of PH generated by hypoxic stimulation. A pulmonary hypertensive state was successfully induced by 2 wk after surgery. However, the morphologic analysis demonstrated that pulmonary vascular muscularization, as evaluated using right ventricular systolic pressure and RV/(LV + S), was not significantly increased until 4 wk postoperatively. When mice from the new model and the hypoxic model were compared, no significant differences were observed in any of the evaluated indices. High-flow PH can be induced within 4 wk after ligation of the right pulmonary artery, which is easily performed in mice. Such mice can be used as a model of high-flow PH. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Eccentric-exercise induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Aldred, S.; Bosch, J.A.; Wadley, A.J.; Veldhuijzen van Zanten, J.J.C.S.

    2013-01-01

    Mental stress has been identified as a trigger of myocardial infarction (MI), with inflammation and vascular responses to mental stress independently implicated as contributing factors. This study examined whether inflammation moderates the vascular responses to mental stress. Eighteen healthy male

  7. Eccentric-exercise induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Aldred, S.; Bosch, J.A.; Wadley, A.J.; Veldhuijzen van Zanten, J.J.C.S.

    2013-01-01

    Mental stress has been identified as a trigger of myocardial infarction (MI), with inflammation and vascular responses to mental stress independently implicated as contributing factors. This study examined whether inflammation moderates the vascular responses to mental stress. Eighteen healthy male

  8. Vascular endothelial growth factor induced angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    Huaijun Liu; Jiping Yang; Fenghai Liu; Qiang Zhang; Hui Li

    2006-01-01

    BACKGROUND: Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor (VEGF) on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic.OBJECTIVE: To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia.DESIGN: A randomized controlled animal trial.SETTING: Department of Medical Imaging, Second Hospital of Hebei Medical University.MATERIALS: Sixty-five healthy male New Zealand rabbits of clean degree, weighing (2.6±0.2) kg, aged4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia (Beijing Zhongshan Company), recombinant VEGF165 (Peprotech Company, USA), biotinylated second antibody and ABC compound (Wuhan Boster Company) were applied.METHODS: The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy,Second Hospital of Hebei Medical University from May to August in 2005. ① The rabbits were randomly divided into three groups: sham-operated group (n=15), control group (n=25) and VEGF-treated group(n=25). In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165(2.5 mg/L) was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabobserved on the 3rd, 7th, 14th, 28th and 70th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The

  9. (-)-Epigallocatechin gallate inhibits TNF-α-induced PAI-1 production in vascular endothelial cells.

    Science.gov (United States)

    Cao, Yanli; Wang, Difei; Wang, Xiaoli; Zhang, Jin; Shan, Zhongyan; Teng, Weiping

    2013-11-01

    : (-)-Epigallocatechin gallate (EGCG), the major catechin derived from green tea, reduces the incidence of cardiovascular diseases such as atherosclerosis. Plasminogen activator inhibitor-1 (PAI-1) accelerates thrombus formation upon ruptured atherosclerotic plaques. However, it is not known whether or not EGCG inhibits PAI-1 production induced by tumor necrosis factor-α (TNF-α) in endothelial cells. This study tested the hypothesis that EGCG might have an inhibitory effect on PAI-1 production induced by TNF-α. Human umbilical vein endothelial cells were cultured and incubated with TNF-α and/or EGCG. The expression of p-extracellular regulated protein kinases (p-ERK1/2) and tumor necrosis factor receptor (TNFR1) protein was quantified by Western blotting, and PAI-1 levels were measured by enzyme-linked immunosorbent assay. The results showed that TNF-α increased PAI-1 production in both a dose-dependent and time-dependent manner, and EGCG prevented TNF-α-mediated PAI-1 production and reduced phosphorylation of ERK1/2. The ERK1/2 inhibitor, PD98059 (20 μmol/L), downregulated TNF-α-induced PAI-1 expression 57.69 ± 2.46% (P TNF-α stimulation resulted in a significant decrease in TNFR1, an effect that was abolished by pretreatment with EGCG. These results suggest that EGCG could provide vascular benefits in inflammatory cardiovascular diseases such as decreased thrombus formation associated with ruptured atherosclerotic plaques.

  10. Panax notoginseng Saponins Attenuate Phenotype Switching of Vascular Smooth Muscle Cells Induced by Notch3 Silencing

    Science.gov (United States)

    Liu, Nan; Shan, Dazhi; Li, Ying; Chen, Hui; Gao, Yonghong; Huang, Yonghua

    2015-01-01

    Panax notoginseng saponins (PNS) could maintain vascular smooth muscle cells (VSMCs) in stable phenotypes so as to keep blood vessel elasticity as well as prevent failing in endovascular treatment with stent. Downregulation of Notch3 expression in VSMCs could influence the phenotype of VSMCs under pathologic status. However, whether PNS is able to attenuate the Notch3 silencing induced phenotype switching of VSMCs remains poorly understood. Primary human VSMCs were transfected with a plasmid containing a small interfering RNA (siRNA) against Notch3 and then exposed to different doses of PNS. The control groups included cells not receiving any treatment and cells transfected with a control siRNA. Phenotypic switching was evaluated by observing cell morphology with confocal microscopy, as well as examining α-SM-actin, SM22α, and OPN using Western blot. Downregulated Notch3 with a siRNA induced apparent phenotype switching, as reflected by morphologic changes, decreased expression of α-SM-actin and SM22α and increased expression of OPN. These changes were inhibited by PNS in a dose-dependent manner. The phenotype switching of VSMCs induced by Notch3 knockdown could be inhibited by PNS in a dose-dependent manner. Our study provided new evidence for searching effective drug for amending stability of atherosclerotic disease. PMID:26539217

  11. Panax notoginseng Saponins Attenuate Phenotype Switching of Vascular Smooth Muscle Cells Induced by Notch3 Silencing

    Directory of Open Access Journals (Sweden)

    Nan Liu

    2015-01-01

    Full Text Available Panax notoginseng saponins (PNS could maintain vascular smooth muscle cells (VSMCs in stable phenotypes so as to keep blood vessel elasticity as well as prevent failing in endovascular treatment with stent. Downregulation of Notch3 expression in VSMCs could influence the phenotype of VSMCs under pathologic status. However, whether PNS is able to attenuate the Notch3 silencing induced phenotype switching of VSMCs remains poorly understood. Primary human VSMCs were transfected with a plasmid containing a small interfering RNA (siRNA against Notch3 and then exposed to different doses of PNS. The control groups included cells not receiving any treatment and cells transfected with a control siRNA. Phenotypic switching was evaluated by observing cell morphology with confocal microscopy, as well as examining α-SM-actin, SM22α, and OPN using Western blot. Downregulated Notch3 with a siRNA induced apparent phenotype switching, as reflected by morphologic changes, decreased expression of α-SM-actin and SM22α and increased expression of OPN. These changes were inhibited by PNS in a dose-dependent manner. The phenotype switching of VSMCs induced by Notch3 knockdown could be inhibited by PNS in a dose-dependent manner. Our study provided new evidence for searching effective drug for amending stability of atherosclerotic disease.

  12. Vascular smooth muscle cell apoptosis promotes transplant arteriosclerosis through inducing the production of SDF-1α.

    Science.gov (United States)

    Li, J; Liu, S; Li, W; Hu, S; Xiong, J; Shu, X; Hu, Q; Zheng, Q; Song, Z

    2012-08-01

    Transplant arteriosclerosis is a leading cause of late allograft loss. Medial smooth muscle cell (SMC) apoptosis is considered to be an important event in transplant arteriosclerosis. However, the precise contribution of medial SMC apoptosis to transplant arteriosclerosis and the underlying mechanisms remain unclear. We transferred wild-type p53 to induce apoptosis of cultured SMCs. We found that apoptosis induces the production of SDF-1α from apoptotic and neighboring viable cells, resulting in increased SDF-1α in the culture media. Conditioned media from Ltv-p53-transferred SMCs activated PI3K/Akt/mTOR and MAPK/Erk signaling in a SDF-1α-dependent manner and thereby promoted mesenchymal stem cell (MSC) migration and proliferation. In a rat aorta transplantation model, lentivirus-mediated BclxL transfer selectively inhibits medial SMC apoptosis in aortic allografts, resulting in a remarkable decrease of SDF-1α both in allograft media and in blood plasma, associated with diminished recruitment of CD90(+)CD105(+) double-positive cells and impaired neointimal formation. Systemic administration of rapamycin or PD98059 also attenuated MSC recruitment and neointimal formation in the aortic allografts. These results suggest that medial SMC apoptosis is critical for the development of transplant arteriosclerosis through inducing SDF-1α production and that MSC recruitment represents a major component of vascular remodeling, constituting a relevant target and mechanism for therapeutic interventions.

  13. Effect of C-myc Antisense Oligodeoxynucleotides on Hypoxia-induced Proliferation of Pulmonary Vascular Pericytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA,3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P<0.01), and elevate 3H-thymidine incorporation of PC (P<0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P<0.05), and 3H-thymidine incorporation of PC (P<0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

  14. Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy.

    Science.gov (United States)

    Zhang, Lu; Wang, XueQin; Miao, YiMing; Chen, ZhiQiang; Qiang, PengFei; Cui, LiuQing; Jing, Hongjuan; Guo, YuQi

    2016-03-01

    Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe3O4NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe3O4NPs (B-Fe3O4NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe3O4NPs did not induce cell death within 24h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe3O4NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe3O4NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe3O4NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe3O4NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe3O4NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe3O4NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation.

  15. AMP-Activated Protein Kinase α2 in Neutrophils Regulates Vascular Repair via Hypoxia-Inducible Factor-1α and a Network of Proteins Affecting Metabolism and Apoptosis

    Science.gov (United States)

    Abdel Malik, Randa; Zippel, Nina; Frömel, Timo; Heidler, Juliana; Zukunft, Sven; Walzog, Barbara; Ansari, Nariman; Pampaloni, Francesco; Wingert, Susanne; Rieger, Michael A.; Wittig, Ilka; Fisslthaler, Beate

    2017-01-01

    Rationale: The AMP-activated protein kinase (AMPK) is stimulated by hypoxia, and although the AMPKα1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPKα2 subunit in vascular repair. Objective: To determine the role of the AMPKα2 subunit in vascular repair. Methods and Results: Recovery of blood flow after femoral artery ligation was impaired (>80%) in AMPKα2−/− versus wild-type mice, a phenotype reproduced in mice lacking AMPKα2 in myeloid cells (AMPKα2ΔMC). Three days after ligation, neutrophil infiltration into ischemic limbs of AMPKα2ΔMC mice was lower than that in wild-type mice despite being higher after 24 hours. Neutrophil survival in ischemic tissue is required to attract monocytes that contribute to the angiogenic response. Indeed, apoptosis was increased in hypoxic neutrophils from AMPKα2ΔMC mice, fewer monocytes were recruited, and gene array analysis revealed attenuated expression of proangiogenic proteins in ischemic AMPKα2ΔMC hindlimbs. Many angiogenic growth factors are regulated by hypoxia-inducible factor, and hypoxia-inducible factor-1α induction was attenuated in AMPKα2-deficient cells and accompanied by its enhanced hydroxylation. Also, fewer proteins were regulated by hypoxia in neutrophils from AMPKα2ΔMC mice. Mechanistically, isocitrate dehydrogenase expression and the production of α-ketoglutarate, which negatively regulate hypoxia-inducible factor-1α stability, were attenuated in neutrophils from wild-type mice but remained elevated in cells from AMPKα2ΔMC mice. Conclusions: AMPKα2 regulates α-ketoglutarate generation, hypoxia-inducible factor-1α stability, and neutrophil survival, which in turn determine further myeloid cell recruitment and repair potential. The activation of AMPKα2 in neutrophils is a decisive event in the initiation of vascular repair after ischemia. PMID:27777247

  16. Ginseng Extracts Restore High-Glucose Induced Vascular Dysfunctions by Altering Triglyceride Metabolism and Downregulation of Atherosclerosis-Related Genes

    Directory of Open Access Journals (Sweden)

    Gabriel Hoi-huen Chan

    2013-01-01

    Full Text Available The king of herbs, Panax ginseng, has been used widely as a therapeutic agent vis-à-vis its active pharmacological and physiological effects. Based on Chinese pharmacopeia Ben Cao Gang Mu and various pieces of literature, Panax ginseng was believed to exert active vascular protective effects through its antiobesity and anti-inflammation properties. We investigated the vascular protective effects of ginseng by administrating ginseng extracts to rats after the induction of diabetes. We found that Panax ginseng can restore diabetes-induced impaired vasorelaxation and can reduce serum triglyceride but not cholesterol level in the diabetic rats. The ginseng extracts also suppressed the expression of atherosclerosis-related genes and altered the expression of lipid-related genes. The results provide evidence that Panax ginseng improves vascular dysfunction induced by diabetes and the protective effects may possibly be due to the downregulation of atherosclerosis-related genes and altered lipid metabolism, which help to restore normal endothelium functions.

  17. Attenuation of endothelin-1-induced calcium response by tyrosine kinase inhibitors in vascular smooth muscle cells.

    Science.gov (United States)

    Liu, C Y; Sturek, M

    1996-06-01

    Although tyrosine kinases play an important role in cell growth and have been implicated in regulation of smooth muscle contraction, their role in agonist-induced myoplasmic Ca2+ responses is unclear. We examined effects of the tyrosine kinase inhibitors genistein and methyl 2,5-dihydroxycinnamate (MDHC) on the endothelin-1 (ET-1)-induced Ca2+ response and determined underlying mechanisms for the effects. Freshly isolated smooth muscle cells from porcine coronary arteries were loaded with fura 2 ester, and myoplasmic free Ca2+ (Ca2+ (m)) concentration was estimated with fura 2 microfluorometry. Both genistein and MDHC inhibited the initial transient Cam2+ response to ET by 54 and 81%, respectively (P latent period from ET-1 application to the beginning of the Cam2+ response being increased from 1.08 +/- 0.17 to 2.65 +/- 0.52 min (P < 0.05). In the absence of extracellular Ca2+, genistein inhibited the ET-1-induced Cam2+ response by 93% (P < 0.05). The Cam2+ responses to caffeine (5 mM) or inositol trisphosphate (IP3) applied intracellularly via a patch-clamp pipette were not affected by genistein. Both genistein and MDHC also abolished the sustained Cam2+ response to ET-1. However, the Cam2+ response to depolarization by 80 mM K+ was not inhibited by MDHC and only inhibited 22% by genistein (P < 0.05). These results indicate that 1) activation of tyrosine kinases is an important regulatory mechanism for the ET-1-induced Cam2+ response in vascular smooth muscle and 2) tyrosine kinases mediate ET-1-induced Ca2+ release with no direct effect on IP3-mediated Ca2+ release. Thus ET-1-mediated signaling upstream of IP3 interaction with the Ca2+ stores is regulated by tyrosine kinases.

  18. An investigation of the most Flow Inducing Genres

    Directory of Open Access Journals (Sweden)

    Behzad Ghonsooly

    2014-05-01

    Full Text Available The present study aims at examining the extent to which three discourse genres of descriptive, expository, and narrative would be flow inducing. In other words, it attempts to testify the role of the text in promoting optimal experience on the one hand, and to identify which discourse genre would be the most flow inducing, on the other hand. To this end, a community sample of 60 participants comprising of 16 males and 44 females from various English language institutes in Mashhad, volunteered to take part in the study by reading three texts of TOEFL containing the expository, narrative, and descriptive genres. After each reading the respondents were asked to reflect on their flow experience through filling in the Flow Perception Questionnaire (Egbert, 2003. The researchers investigated flow differences across genres by employing repeated measures ANOVA. The results revealed that flow occurred during the reading of descriptive, narrative, and expository genres; however, there were significant differences in terms of the flow scores engendered by the variations across these genres. The results of the data analysis reported the descriptive genre as the most flow inducing discourse genre.

  19. Diet-induced changes in subcutaneous adipose tissue blood flow in man: effect of beta-adrenoceptor inhibition

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Astrup, A

    1990-01-01

    The effect of a carbohydrate-rich meal on subcutaneous adipose tissue blood flow was studied with and without continuous i.v. infusion of propranolol in healthy volunteers. The subcutaneous adipose tissue blood flow was measured with the 133Xe washout method in three different locations...... it in the forearm. This indicates that the mechanism for the flow increase is elicited by a stimulation of vascular beta-adrenoceptors in the subcutaneous adipose tissue, since the beta-adrenoceptor inhibition did not affect the overall metabolic and hormonal responses to the meal.......: the forearm, the thigh and the abdomen. The subjects were given a meal consisting of white bread, jam, honey and apple juice (about 2300 kJ). The meal induced a twofold increase in blood flow in the examined tissues. Propranolol abolished the flow increase in the thigh and the abdomen and reduced...

  20. Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

    Science.gov (United States)

    Zhao, Gaiping; Wu, Jie; Xu, Shixiong; Collins, M. W.; Long, Quan; König, Carola S.; Jiang, Yuping; Wang, Jian; Padhani, A. R.

    2007-10-01

    A coupled intravascular transvascular interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille’s law and Darcy’s law, respectively, transvascular flow is described by Starling’s law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

  1. SIMULATIONS OF FLOW INDUCED CORROSION IN API DRILLPIPE CONNECTOR

    Institute of Scientific and Technical Information of China (English)

    ZHU Hong-jun; LIN Yuan-hua; ZENG De-zhi; YAN Ren-tian

    2011-01-01

    Drillpipe failure is an outstanding issue in drilling engineering,often involving great financial losses.In view of the special features of the flow channel in the high failure zone,this article analyzes the drillpipe failure mechanism from the point of view of flow induced corrosion.Based on the Eulerian-Langrangian method and the discrete phase model,a numerical simulation method is used to investigate the flows of the drilling fluid in the drillpipe connector during the operation of three typical drilling methods (mud drilling,air drilling and foam drilling).From the flow field in the drillpipe connector,especially,the velocity and pressure distributions in the threaded nipple and the thickened intermediate belt,one may detect the existence of the flow induced corrosion.Then,some structural optimization measures for the drillpipe connector are proposed,and the optimization effects are compared.

  2. Formation of step bunches induced by flow in solution

    OpenAIRE

    Inaba, Masashi; Sato, Masahide

    2012-01-01

    We study the formation of step bunches induced by flow in solution during growth. In our previous study [M. Inaba and M. Sato: J. Phys. Soc. Jpn. 80 (2011) 074606], we showed that the step-down flow in solution causes bunching. In this research, we study the dependence of step behavior on some parameters. With a slow flow, the separation and coalescence between steps and bunches occur frequently during step bunching. With increasing flow rate, the frequency decreases and tight bunches are for...

  3. Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-07-15

    Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

  4. Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model.

    Science.gov (United States)

    Qin, Bing; Deng, Yunlong

    2015-01-01

    Disturbance of the circadian clock by sleep deprivation has been proposed to be involved in the regulation of inflammation. However, the underlying mechanism of circadian oscillator components in regulating the pro-inflammatory process during sleep deprivation remains poorly understood. Using a sleep deprivation mouse model, we showed here that sleep deprivation increased the expression of pro-inflammatory cytokines expression and decreased the expression of cryptochrome 1 (CRY1) in vascular endothelial cells. Furthermore, the adhesion molecules including intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin were elevated in vascular endothelial cells and the monocytes binding to vascular endothelial cells were also increased by sleep deprivation. Interestingly, overexpression of CRY1 in a mouse model by adenovirus vector significantly inhibited the expression of inflammatory cytokines and adhesion molecules, and NF-κB signal pathway activation, as well as the binding of monocytes to vascular endothelial cells. Using a luciferase reporter assay, we found that CRY1 could repress the transcriptional activity of nuclear factor (NF)-κB in vitro. Subsequently, we demonstrated that overexpression of CRY1 inhibited the basal concentration of cyclic adenosine monophosphate (cAMP), leading to decreased protein kinase A activity, which resulted in decreased phosphorylation of p65. Taken together, these results suggested that the overexpression of CRY1 inhibited sleep deprivation-induced vascular inflammation that might be associated with NF-κB and cAMP/PKA pathways.

  5. Vascular barrier protective effects of orientin and isoorientin in LPS-induced inflammation in vitro and in vivo.

    Science.gov (United States)

    Lee, Wonhwa; Ku, Sae-Kwang; Bae, Jong-Sup

    2014-07-01

    Endothelial cell protein C receptor (EPCR) can be shed from the cell surface, and this process is mediated by tumor necrosis factor-α converting enzyme (TACE), and high levels of soluble EPCR are involved in vascular inflammation. Orientin, one of the C-glycosyl flavonoids, has been known to have anxiolytic and antioxidative activities. However, the effect of orientin on lipopolysaccharide (LPS)-induced inflammatory response has not been studied. Here we investigated the barrier protective effects of orientin against pro-inflammatory responses induced by LPS and the associated signaling pathways. We found that orientin inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to human endothelial cells. Orientin induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced EPCR shedding. Orientin also suppressed LPS-induced hyperpermeability and leukocyte migration in vivo. Furthermore, orientin suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with orientin resulted in reduced LPS-induced lethal endotoxemia. These results suggest that orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

  6. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.

    Science.gov (United States)

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P R

    2016-05-18

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P mobilization by G-CSF or AMD3100 was either increased or unaffected (P mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.

  7. Coriolis-induced cutaneous blood flow increase in the forearm and calf.

    Science.gov (United States)

    Cheung, B; Hofer, K

    2001-04-01

    Using venous occlusion plethysmography, Sunahara et al. reported that Coriolis-induced nausea was accompanied by an increase in forearm blood flow, suggesting a decrease in sympathetic activity to this vascular bed. No significant blood pressure and heart rate changes were observed. Vasodilation of the limbs theoretically impairs orthostatic tolerance, particularly if blood flow is shown to increase simultaneously in the lower limbs. This study examined the latter possibility. Seventeen subjects were exposed to the Coriolis cross-coupling effects induced by 20 RPM yaw rotation, and a simultaneous 45 degrees pitch forward head movement in the sagittal plane every 12 s. Forearm and calf skin blood flow were monitored in real-time using laser Doppler flowmetry (PeriFlux 4001). Our results indicated a significant (p Coriolis cross-coupling across all 15 susceptible subjects. No significant changes in blood pressure and heart rate were observed. Coriolis-induced cardiovascular changes may confound previous reports on reduced G tolerance using ground-based centrifuges that invariably evoke cross-coupling effects.

  8. Mast Cells Induce Vascular Smooth Muscle Cell Apoptosis via a Toll-Like Receptor 4 Activation Pathway.

    NARCIS (Netherlands)

    Dekker, W.K.; Tempel, D.; Bot, I.; Biessen, E.A.; Joosten, L.A.B.; Netea, M.G.; Meer, J.W.M. van der; Cheng, C.; Duckers, H.J.

    2012-01-01

    OBJECTIVE: Activated mast cells (MCs) release chymase, which can induce vascular smooth muscle cell (VSMC) apoptosis leading to plaque destabilization. Because the mechanism through which MCs release chymase in atherosclerosis is unknown, we studied whether MC-associated VSMC apoptosis is regulated

  9. Hemorrhage-induced Vascular Hyporeactivity to Norepinephrine in Select Vasculatures of Rats and the Roles of Nitric Oxide and Endothelin

    Science.gov (United States)

    2003-03-01

    Hepatology 27:755– 764, 1998. 20. Iglarz M, Levy BI, Henrion D: Chronic endothelin-1 induced changes in vascu- lar reactivity in rat resistance...Mitchell JA, Vane JR: Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide

  10. Hypoxia-inducible factor and vascular endothelial growth factor in the neuroretina and retinal blood vessels after retinal ischemia

    DEFF Research Database (Denmark)

    Håkansson, Gisela; Gesslein, Bodil; Gustafsson, Lotta

    2010-01-01

    Retinal ischemia arises from circulatory failure. As the retinal blood vessels are key organs in circulatory failure, our aim was to study the retinal vasculature separately from the neuroretina to elucidate the role of hypoxia-inducible factor (HIF) 1α and 1β and vascular endothelial growth factor...

  11. Protective effect of N-acetylcysteine against nicardipine hydrochloride-induced autophagic cell death of human vascular endothelial cells.

    Science.gov (United States)

    Ochi, Masanori; Tanaka, Yoshiyuki; Toyoda, Hiromu

    2015-01-01

    Nicardipine hydrochloride (NIC) injection has been widely used for emergency treatment of abnormally high blood pressure. However, NIC injection often causes severe peripheral vascular injury. The purpose of the present study was to reduce the NIC-induced cell injury in human vascular endothelial cells by use of clinical agents. The mechanism of NIC-induced cell injury was evaluated by time-lapse microscopic imaging, autophagosome staining with monodansylcadaverine, immunostaining of light chain 3 isoform B (LC-3B) and assessment of cell viability after exposure to NIC with or without an inhibitor of autophagosome formation (3-methyladenine, 3-MA). Results from autophagosome labeling and immunostaining of LC-3B revealed an increase of autophagosomes and LC-3B in NIC-treated cells. NIC-mediated reduction of cell viability was inhibited by 3-methyladenine. Moreover, we found that N-acetylcysteine (NAC) reduced NIC-induced cell injury in human vascular endothelial cells. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy with NAC could contribute to the reduction of NIC-induced vascular injury.

  12. Heme oxygenase-1 alleviates cigarette smoke-induced restenosis after vascular angioplasty by attenuating inflammation in rat model.

    Science.gov (United States)

    Ni, Leng; Wang, Zhanqi; Yang, Genhuan; Li, Tianjia; Liu, Xinnong; Liu, Changwei

    2016-03-14

    Cigarette smoke is not only a profound independent risk factor of atherosclerosis, but also aggravates restenosis after vascular angioplasty. Heme oxygenase-1 (HO-1) is an endogenous antioxidant and cytoprotective enzyme. In this study, we investigated whether HO-1 upregulating by hemin, a potent HO-1 inducer, can protect against cigarette smoke-induced restenosis in rat's carotid arteries after balloon injury. Results showed that cigarette smoke exposure aggravated stenosis of the lumen, promoted infiltration of inflammatory cells, and induced expression of inflammatory cytokines and adhesion molecules after balloon-induced carotid artery injury. HO-1 upregulating by hemin treatment reduced these effects of cigarette smoke, whereas the beneficial effects were abolished in the presence of Zincprotoporphyrin IX, an HO-1 inhibitor. To conclude, hemin has potential therapeutic applications in the restenosis prevention after the smokers' vascular angioplasty. Copyright © 2016. Published by Elsevier Ireland Ltd.

  13. Vascular inward rectifier K+ channels as external K+ sensors in the control of cerebral blood flow.

    Science.gov (United States)

    Longden, Thomas A; Nelson, Mark T

    2015-04-01

    For decades it has been known that external K(+) ions are rapid and potent vasodilators that increase CBF. Recent studies have implicated the local release of K(+) from astrocytic endfeet-which encase the entirety of the parenchymal vasculature-in the dynamic regulation of local CBF during NVC. It has been proposed that the activation of KIR channels in the vascular wall by external K(+) is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular KIR channels are the major extracellular K(+) sensors in the control of CBF. We propose that K(+) is an ideal mediator of NVC, and discuss KIR channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that KIR channels, of the KIR 2 subtype in particular, are present in both the endothelial and SM cells of parenchymal arterioles and propose that this dual positioning of KIR 2 channels increases the robustness of the vasodilation to external K(+), enables the endothelium to be actively engaged in NVC, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF.

  14. Flow-Induced Vibration of Circular Cylindrical Structures

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shoei-Sheng [Argonne National Lab. (ANL), Argonne, IL (United States). Components Technology Division

    1985-06-01

    Flow-induced vibration is a term to denote those phenomena associated with the response of structures placed in or conveying fluid flow. More specifically, the terra covers those cases in which an interaction develops between fluid-dynamic forces and the inertia, damping or elastic forces in the structures. The study of these phenomena draws on three disciplines: (1) structural mechanics, (2) mechanical vibration, and (3) fluid dynamics. The vibration of circular cylinders subject to flow has been known to man since ancient times; the vibration of a wire at its natural frequency in response to vortex shedding was known in ancient Greece as aeolian tones. But systematic studies of the problem were not made until a century ago when Strouhal established the relationship between vortex shedding frequency and flow velocity for a given cylinder diameter. The early research in this area has beer summarized by Zdravkovich (1985) and Goldstein (1965). Flow-induced structural vibration has been experienced in numerous fields, including the aerospace industry, power generation/transmission (turbine blades, heat exchanger tubes, nuclear reactor components), civil engineering (bridges, building, smoke stacks), and undersea technology. The problems have usually been encountered or created accidentally through improper design. In most cases, a structural or mechanical component, designed to meet specific objectives, develops problems when the undesired effects of flow field have not been accounted for in the design. When a flow-induced vibration problem is noted in the design stage, the engineer has different options to eliminate the detrimental vibration. Unfortunately, in many situations, the problems occur after the components are already in operation; the "fix" usually is very costly. Flow-induced vibration comprises complex and diverse phenomena; subcritical vibration of nuclear fuel assemblies, galloping of transmission lines, flutter of pipes conveying fluid, and whirling

  15. Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice

    Science.gov (United States)

    Chen, Cheng-Hsien; Chen, Tso-Hsiao; Wu, Mei-Yi; Chou, Tz-Chong; Chen, Jia-Rung; Wei, Meng-Jun; Lee, San-Liang; Hong, Li-Yu; Zheng, Cai-Mei; Chiu, I-Jen; Lin, Yuh-Feng; Hsu, Ching-Min; Hsu, Yung-Ho

    2017-01-01

    The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury. PMID:28071754

  16. Heparan sulfate proteoglycans mediate Aβ-induced oxidative stress and hypercontractility in cultured vascular smooth muscle cells

    OpenAIRE

    2016-01-01

    Background Substantial evidence suggests that amyloid-β (Aβ) species induce oxidative stress and cerebrovascular (CV) dysfunction in Alzheimer’s disease (AD), potentially contributing to the progressive dementia of this disease. The upstream molecular pathways governing this process, however, are poorly understood. In this report, we examine the role of heparan sulfate proteoglycans (HSPG) in Aβ-induced vascular smooth muscle cell (VSMC) dysfunction in vitro. Results Our results demonstrate t...

  17. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia

    OpenAIRE

    Choi, Dong-Hee; Lee, Kyoung-Hee; Lee, Jongmin

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive def...

  18. Yangxueqingnao particles inhibit rat vascular smooth muscle cell proliferation induced by lysophosphatidic acid

    Institute of Scientific and Technical Information of China (English)

    CAI Wei; XU Yi; CHEN Jun-zhu; HUANG Shu-ru; LU Zhen-ya; WANG Zhan-kun

    2005-01-01

    Objective: To observe the effect of Yangxueqingnao particles on rat vascular smooth muscle cell (VSMC) proliferation induced by lysophosphatidic acid (LPA). Methods: The amount of3H-TdR (3H-thymidine) admixed in cultured rat VSMC was measured and mitogen-activated protein kinase (MAPK) activity and lipid peroxidation end product malondialdehyde (MDA)content of the VSMC were assayed. Results: 1×10-9, 1×10-8, 1×10-7 mol/L LPA in a concentration dependent manner, induced the amount of 3H-TdR admixed, MAP kinase activity, and MDA content of the cultured rat VSMC to increase. However, 5%, 10%,and 15% Yangxueqingnao serum preincubation resulted in a decrease of 23.0%, 42.0%, and 52.0% (P<0.01) respectively in the amount of 3H-TdR admixed, a decline in VSMC MAP kinase activity of 13.9% (P<0.05), 29.6% (P<0.01), and 48.9% (P<0.01)respectively, and also, a decrease in MDA content of VSMC of 19.4%, 24.7%, and 43.2% (P<0.01) respectively, in the 1×10-7mol/L LPA-treated VSMC. Conclusions: LPA activates the proliferation and lipid peroxidation of VSMC in a concentration dependent manner. The LPA-induced VSMC proliferation is related to the activity of MAP kinases, enzymes involved in an intracellular signalling pathway. The results of the present study showed that Yangxueqingnao particles can effectively inhibit LPA-induced VSMC proliferation, MAP kinase activation, and reduce lipid peroxidative lesion.

  19. Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Lin CHANG; Jian-xin XU; Jing ZHAO; Yong-zheng PANG; Chao-shu TANG; Yong-fen QI

    2004-01-01

    AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS) - hydrogen peroxide (H2O2) and superoxide anion (O2- )were measured with luminol or lucigenin chemiluminescences method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocystenie, was increased (P<0.01 vs control), and it was markedly inhibited when co-incubated with taurine (P<0.01). Homocysteine induced H2O2 generation from VSMC in a concentration dependent manner (P<0.01 vs control). However, taurine (5, 10, and 20 mmol/L) significantly antagonized 0.5 mmol/L homocysteine-induced H2O2 generation in VSMC in a concentration dependent manner (P<0.01 vs homocysteine alone group), although taurine itself did not alter the H2O2 generation in VSMC (P>0.05 vs control).In this study, the superoxide anion in VSMC was not detectable by chemiluminent method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition,co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

  20. Wave-Induced Groundwater Flows in a Freshwater Beach Aquifer

    Science.gov (United States)

    Malott, S. S.; Robinson, C. E.; O'Carroll, D. M.

    2014-12-01

    Wave-induced recirculation across the sediment-water interface can impact the transport of pollutants through a beach aquifer and their ultimate flux into coastal waters. The fate of nutrients (e.g. from septic and agricultural sources) and fecal indicator bacteria (e.g. E. coil) near the sediment-water interface are of particular concern as these pollutants often lead to degradation of recreational water quality and nearshore ecosystems. This paper presents detailed field measurements of groundwater flows in a freshwater beach aquifer on Lake Huron over periods of intensified wave conditions. Quantifying wave-driven processes in a freshwater beach aquifer enables wave effects to be studied in isolation from density and tidal effects that complicate groundwater flows in marine beaches. Water exchange across the sediment-water interface and groundwater flow patterns were measured using groundwater wells, arrays of vertically nested pressure transducers and manometers. Results show that wave action induces rapid infiltration/exfiltration across the sediment-water interface and a larger recirculation cell through the beach aquifer. Field data is used to validate a numerical groundwater model of wave-induced groundwater flows. While prior studies have simulated the effects of waves on beach groundwater flows, this study is the first attempt to validate these sophisticated modeling approaches. Finally, field data illustrating the impact of wave-induced groundwater flows on nutrient and bacteria fate and transport in beach aquifers will also be presented.

  1. Fibro-Vascular Coupling in the Control of Cochlear Blood Flow

    OpenAIRE

    Min Dai; Xiaorui Shi

    2011-01-01

    BACKGROUND: Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained. METHODOLOGY/PRINCIPAL FINDINGS: We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte...

  2. Autophagy inhibits PDGF-BB-induced calcification in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    PEI Qian-qian; MEI Han; ZHANG Xu-hui; DONG Li-hua

    2016-01-01

    AIM:To investigate the relationship between autophagy and calcification in vascular smooth muscle cells ( VSMCs) after platelet-derived growth factor (PDGF)-BB stimulation.METHODS:Cultured VSMCs were stimulated with PDGF-BB for different time, the expression of vascular calcification-related proteins and autophagy-related proteins were detected by Western blot .The interaction be-tween Beclin1 and PI3KC3 was detected by co-immunoprecipitation.RESULTS: The expression of BMP2 and ALP showed a trend from decline to rise.ALP slumped at 12 h, and BMP2 slumped at 6 h.Moreover, the expression of Beclin-1 showed a trend from rise to decline, and peaked at 12 h.The conversion of LC3-ⅠtoⅡincreased in a time-dependent manner , and peaked at 24 h.The ex-pression of BMP2 and ALP was increased in VSMCs incubated with PDGF-BB and autophagy inhibitor 3-MA, compared with PDGF-BB-stimulated VSMCs.Furthermore, the interaction between Beclin1 and PI3KC3 was enhanced at 6 h after PDGF-BB stimulated, peaked at 12 h, and kept in high level at 24 h.Moreover, the phosphorylation level of Beclin 1 was enhanced by PDGF-BB stimulation, and peaked at 6 h.CONCLUSION:Our findings demonstrate that PDGF-BB-induced autophagy inhibits VSMC calcification by en-hancing Beclin1 phosphorylation and interaction between Beclin 1 and PI3KC3.

  3. Interleukin-1beta induced vascular permeability is dependent on induction of endothelial tissue factor (TF) activity.

    Science.gov (United States)

    Puhlmann, Markus; Weinreich, David M; Farma, Jeffrey M; Carroll, Nancy M; Turner, Ewa M; Alexander, H Richard

    2005-09-30

    IL-1beta is a pleotropic cytokine that may mediate increased procoagulant activity and permeability in endothelial tissue during inflammatory conditions. The procoagulant effects of IL-1beta are mediated through induction of tissue factor (TF) but its alterations on vascular permeability are not well characterized. We found that IL-1beta induced a rapid and dose-dependent increase in TF activity in human umbilical vein endothelial cells (ECs) under routine culture conditions. However, IL-1beta caused a rapid and marked increase in permeability across confluent EC monolayers using a two-compartment in vitro model only in the presence of factor VIII-deficient plasma that was completely abrogated by neutralizing anti-TF antibody pre-treatment. In vitro permeability was associated with loss of EC surface expression of VE-cadherin and contraction of F-actin cytoskeletal elements that resulted in EC intercellular gap formation. These data demonstrate that IL-1beta induces marked changes in permeability across activated endothelium via a TF dependent mechanism and suggest that modulation of TF activity may represent a strategy to treat various acute and chronic inflammatory conditions mediated by this cytokine.

  4. Interleukin-1β induced vascular permeability is dependent on induction of endothelial Tissue Factor (TF activity

    Directory of Open Access Journals (Sweden)

    Turner Ewa M

    2005-09-01

    Full Text Available Abstract IL-1β is a pleotropic cytokine that may mediate increased procoagulant activity and permeability in endothelial tissue during inflammatory conditions. The procoagulant effects of IL-1β are mediated through induction of tissue factor (TF but its alterations on vascular permeability are not well characterized. We found that IL-1β induced a rapid and dose-dependent increase in TF activity in human umbilical vein endothelial cells (ECs under routine culture conditions. However, IL-1β caused a rapid and marked increase in permeability across confluent EC monolayers using a two-compartment in vitro model only in the presence of factor VIII-deficient plasma that was completely abrogated by neutralizing anti-TF antibody pre-treatment. In vitro permeability was associated with loss of EC surface expression of VE-cadherin and contraction of F-actin cytoskeletal elements that resulted in EC intercellular gap formation. These data demonstrate that IL-1β induces marked changes in permeability across activated endothelium via a TF dependent mechanism and suggest that modulation of TF activity may represent a strategy to treat various acute and chronic inflammatory conditions mediated by this cytokine.

  5. Soft X-ray induced chemical modification of polysaccharides in vascular plant cell walls

    Energy Technology Data Exchange (ETDEWEB)

    Cody, George D. [Geophysical Laboratory, Carnegie Institution of Washington, 5251 Broad Branch Rd. NW, Washington, DC 20015 (United States)], E-mail: cody@gl.ciw.edu; Brandes, Jay [Skidaway Institute of Oceangraphy, Savannah, GA (United States); Jacobsen, Chris; Wirick, Susan [Department of Physics, State University of New York, Stony Brook, NY (United States)

    2009-03-15

    Scanning transmission X-ray microscopy and micro carbon X-ray Absorption Near Edge Spectroscopy (C-XANES) can provide quantitative information regarding the distribution of the biopolymers cellulose, hemicellulose, and lignin in vascular plant cell walls. In the case of angiosperms, flowering plants, C-XANES may also be able to distinguish variations in lignin monomer distributions throughout the cell wall. Polysaccharides are susceptible to soft X-ray irradiation induced chemical transformations that may complicate spectral analysis. The stability of a model polysaccharide, cellulose acetate, to variable doses of soft X-rays under conditions optimized for high quality C-XANES spectroscopy was investigated. The primary chemical effect of soft X-ray irradiation on cellulose acetate involves mass loss coincident with de-acetylation. A lesser amount of vinyl ketone formation also occurs. Reduction in irradiation dose via defocusing does enable high quality pristine spectra to be obtained. Radiation induced chemical modification studies of oak cell wall reveals that cellulose and hemicellulose are less labile to chemical modification than cellulose acetate. Strategies for obtaining pristine C-XANES spectra of polysaccharides are presented.

  6. Delayed Onset Vascular Stiffening Induced by Eccentric Resistance Exercise and Downhill Running.

    Science.gov (United States)

    Lin, Hsin-Fu; Chou, Chun-Chung; Cheng, Hao-Min; Tanaka, Hirofumi

    2017-07-01

    Eccentric exercise induces muscle stiffening and soreness as well as unfavorable changes in macrovascular function. We tested the hypothesis that systemic eccentric exercise could evoke greater arterial stiffening than local eccentric resistance exercise. Twenty healthy young men were randomly assigned into either the downhill running (DR) and the eccentric resistance exercise (RE) group followed by a crossover design with an exercise and sham control trial. Carotid-femoral pulse wave velocity (cfPWV), central hemodynamic measures, and biomarkers were obtained. Muscle soreness and plasma creatine kinase concentrations increased similarly after exercise in both groups. The cfPWV increased significantly at 48 hours post-exercise in both groups and remained elevated at 72 hours in DR. C-reactive protein (CRP) was elevated at 24 and 48 hours in DR, and 48 hours in RE. The increases in cfPWV were associated with the corresponding elevations in CRP in DR (r = 0.70, P < 0.05). There were no changes in arterial wave reflection measures. Both systemic and localized eccentric exercise modes induced delayed onset vascular stiffening with more prolonged changes observed in downhill running. The effect on arterial stiffening was associated, at least in part, with systemic inflammatory responses.

  7. Modelling Cerebral Blood Flow and Temperature Using a Vascular Porous Model

    Science.gov (United States)

    Blowers, Stephen; Thrippleton, Michael; Marshall, Ian; Harris, Bridget; Andrews, Peter; Valluri, Prashant

    2016-11-01

    Macro-modelling of cerebral blood flow can assist in determining the impact of temperature intervention to reduce permanent tissue damage during instances of brain trauma. Here we present a 3D two phase fluid-porous model for simulating blood flow through the capillary region linked to intersecting 1D arterial and venous vessel trees. This combined vasculature porous (VaPor) model simulates both flow and energy balances, including heat from metabolism, using a vasculature extracted from MRI data which are expanded upon using a tree generation algorithm. Validation of temperature balance has been achieved using rodent brain data. Direct flow validation is not as straight forward due to the method used in determining regional cerebral blood flow (rCBF). In-vivo measurements are achieved using a tracer, which disagree with direct measurements of simulated flow. However, by modelling a virtual tracer, rCBF values are obtained that agree with those found in literature. Temperature profiles generated with the VaPor model show a reduction in core brain temperature after cooling the scalp not seen previously in other models.

  8. Increased Nitric Oxide Bioavailability and Decreased Sympathetic Modulation Are Involved in Vascular Adjustments Induced by Low-Intensity Resistance Training.

    Science.gov (United States)

    Macedo, Fabrício N; Mesquita, Thassio R R; Melo, Vitor U; Mota, Marcelo M; Silva, Tharciano L T B; Santana, Michael N; Oliveira, Larissa R; Santos, Robervan V; Miguel Dos Santos, Rodrigo; Lauton-Santos, Sandra; Santos, Marcio R V; Barreto, Andre S; Santana-Filho, Valter J

    2016-01-01

    Resistance training is one of the most common kind of exercise used nowadays. Long-term high-intensity resistance training are associated with deleterious effects on vascular adjustments. On the other hand, is unclear whether low-intensity resistance training (LI-RT) is able to induce systemic changes in vascular tone. Thus, we aimed to evaluate the effects of chronic LI-RT on endothelial nitric oxide (NO) bioavailability of mesenteric artery and cardiovascular autonomic modulation in healthy rats. Wistar animals were divided into two groups: exercised (Ex) and sedentary (SED) rats submitted to the resistance (40% of 1RM) or fictitious training for 8 weeks, respectively. After LI-RT, hemodynamic measurements and cardiovascular autonomic modulation by spectral analysis were evaluated. Vascular reactivity, NO production and protein expression of endothelial and neuronal nitric oxide synthase isoforms (eNOS and nNOS, respectively) were evaluated in mesenteric artery. In addition, cardiac superoxide anion production and ventricle morphological changes were also assessed. In vivo measurements revealed a reduction in mean arterial pressure and heart rate after 8 weeks of LI-RT. In vitro studies showed an increased acetylcholine (ACh)-induced vasorelaxation and greater NOS dependence in Ex than SED rats. Hence, decreased phenylephrine-induced vasoconstriction was found in Ex rats. Accordingly, LI-RT increased the NO bioavailability under basal and ACh stimulation conditions, associated with upregulation of eNOS and nNOS protein expression in mesenteric artery. Regarding autonomic control, LI-RT increased spontaneous baroreflex sensitivity, which was associated to reduction in both, cardiac and vascular sympathetic modulation. No changes in cardiac superoxide anion or left ventricle morphometric parameters after LI-RT were observed. In summary, these results suggest that RT promotes beneficial vascular adjustments favoring augmented endothelial NO bioavailability and

  9. Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Lu, E-mail: chaperones@163.com [College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001 (China); Wang, XueQin; Miao, YiMing; Chen, ZhiQiang; Qiang, PengFei; Cui, LiuQing; Jing, Hongjuan [College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001 (China); Guo, YuQi [Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China)

    2016-03-05

    Highlights: • B-Fe{sub 3}O{sub 4}NPs did not induce cell apoptosis or necrosis in HUVECs within 24 h. • B-Fe{sub 3}O{sub 4}NPs induced HUVEC dysfunction and inflammation. • B-Fe{sub 3}O{sub 4}NPs induced enhanced autophagic activity and blockade of autophagy flux. • Suppression of autophagy dysfunction attenuated B-Fe{sub 3}O{sub 4}NP-induced HUVEC dysfunction. - Abstract: Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe{sub 3}O{sub 4}NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe{sub 3}O{sub 4}NPs (B-Fe{sub 3}O{sub 4}NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe{sub 3}O{sub 4}NPs did not induce cell death within 24 h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe{sub 3}O{sub 4}NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe{sub 3}O{sub 4}NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe{sub 3}O{sub 4}NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe{sub 3}O{sub 4}NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe{sub 3}O{sub 4}NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe{sub 3}O{sub 4}NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation.

  10. Vascular Tone Regulation Induced by C-Type Natriuretic Peptide: Differences in Endothelium-Dependent and -Independent Mechanisms Involved in Normotensive and Spontaneously Hypertensive Rats

    Science.gov (United States)

    Caniffi, Carolina; Cerniello, Flavia M.; Gobetto, María N.; Sueiro, María L.; Arranz, Cristina

    2016-01-01

    Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one in both groups. In contrast, blockade of cyclooxygenase or subtype 2 bradykinin receptor increased CNP potency only in SHR. In both Wistar and SHR, CNP relaxation was blunted by tetraethylammonium and partially inhibited by BaCl2 and iberiotoxin, indicating that it was due to opening of the Kir and BKCa channels. However, SHR seem to be more sensitive to Kir channel blockade and less sensitive to BKCa channel blockade than normotensive rats. In addition, CNP decreases HVR in Wistar and SHR, but the effect of CNP increasing blood flow was more marked in SHR. We conclude that CNP induces aorta relaxation by activation of the nitric oxide system and opening of potassium channels, but the response to the peptide is impaired in conductance vessel of hypertensive rats. PMID:27936197

  11. Compression-induced hyperaemia in the rabbit masseter muscle: a model to investigate vascular mechano-sensitivity of skeletal muscle.

    Science.gov (United States)

    Turturici, Marco; Roatta, Silvestro

    2013-03-01

    Recent evidence suggests that the mechano-sensitivity of the vascular network may underlie rapid dilatory events in skeletal muscles. Previous investigations have been mostly based either on in vitro or on whole-limb studies, neither preparation allowing one to assess the musculo-vascular specificity under physiological conditions. The aim of this work is to characterize the mechano-sensitivity of an exclusively-muscular vascular bed in vivo. In five anesthetized rabbits, muscle blood flow was continuously monitored in the masseteric artery, bilaterally (n = 10). Hyperaemic responses were evoked by compressive stimuli of different extent (50, 100 and 200 mm Hg) and duration (0.5, 1, 2 and 5 s) exerted by a servo-controlled motor on the masseter muscle. Peak amplitude of the hyperaemic response ranged from 340 ± 30% of baseline (at 50 mm Hg) to 459 ± 57% (at 200 mm Hg) (P < 0.05), did not depend on stimulus duration and exhibited very good reliability (ICC = 0.98) when reassessed at 30 min intervals. The time course of the response depended neither on applied pressure nor on the duration of the stimulus. In conclusion, for its high sensitivity and reliability this technique is adequate to characterize mechano-vascular reactivity and may prove useful in the investigation of the underlying mechanisms, with implications in the control of vascular tone and blood pressure in health and disease.

  12. Reduced endothelial NO-cGMP vascular relaxation pathway during TNF-alpha-induced hypertension in pregnant rats.

    Science.gov (United States)

    Davis, Justin R; Giardina, Jena B; Green, Gachavis M; Alexander, Barbara T; Granger, Joey P; Khalil, Raouf A

    2002-02-01

    Placental ischemia during pregnancy is thought to release cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to the increased vascular resistance associated with pregnancy-induced hypertension. We have reported that a chronic twofold elevation in plasma TNF-alpha increases blood pressure in pregnant but not in virgin rats; however, the vascular mechanisms are unclear. We tested the hypothesis that increasing plasma TNF-alpha during pregnancy impairs endothelium-dependent vascular relaxation and enhances vascular reactivity. Active stress was measured in aortic strips of virgin and late-pregnant Sprague-Dawley rats untreated or infused with TNF-alpha (200 ng x kg(-1) x day(-1) for 5 days) to increase plasma level twofold. Phenylephrine (Phe) increased active stress to a maximum of 4.2 +/- 0.4 x 10(3) and 9.9 +/- 0.7 x 10(3) N/m2 in control pregnant and TNF-alpha-infused pregnant rats, respectively. Removal of the endothelium enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. In endothelium-intact strips, ACh caused greater relaxation of Phe contraction in control than in TNF-alpha-infused pregnant rats. Basal and ACh-induced nitrite/nitrate production was less in TNF-alpha-infused than in control pregnant rats. Pretreatment of vascular strips with 100 microM N(G)-nitro-L-arginine methyl ester, to inhibit nitric oxide (NO) synthase, or 1 microM 1H-[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one, to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. Phe contraction and ACh relaxation were not significantly different between control and TNF-alpha-infused virgin rats. Thus an endothelium-dependent NO-cGMP-mediated vascular relaxation pathway is inhibited in late-pregnant rats infused with TNF-alpha. The results support a role for TNF-alpha as one possible mediator of the increased vascular resistance

  13. Inhibition of rac1 reduces PDGF-induced reactive oxygen species and proliferation in vascular smooth muscle cells.

    OpenAIRE

    2001-01-01

    In vascular smooth muscle cells, reactive oxygen species (ROS) were known to mediate platelet-derived growth factor (PDGF)-induced cell proliferation and NADH/NADPH oxidase is the major source of ROS. NADH/NADPH oxidase is controlled by rac1 in non-phagocytic cells. In this study, we examined whether the inhibition of rac1 by adenoviral-mediated gene transfer of a dominant negative rac1 gene product (Ad.N17rac1) could reduce the proliferation of rat aortic vascular smooth muscle cells (RASMC)...

  14. Manipulation of the HIF–Vegf pathway rescues methyl tert-butyl ether (MTBE)-induced vascular lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bonventre, Josephine A., E-mail: josephine.bonventre@oregonstate.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States); Oregon State University, Department of Environmental and Molecular Toxicology, 1011 Agricultural and Life Sciences Bldg, Corvallis, OR 97331 (United States); Kung, Tiffany S., E-mail: tiffany.kung@rutgers.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States); White, Lori A., E-mail: lawhite@aesop.rutgers.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States); Cooper, Keith R., E-mail: cooper@aesop.rutgers.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States)

    2013-12-15

    Methyl tert-butyl ether (MTBE) has been shown to be specifically anti-angiogenic in piscine and mammalian model systems at concentrations that appear non-toxic in other organ systems. The mechanism by which MTBE targets developing vascular structures is unknown. A global transcriptome analysis of zebrafish embryos developmentally exposed to 0.00625–5 mM MTBE suggested that hypoxia inducible factor (HIF)-regulated pathways were affected. HIF-driven angiogenesis via vascular endothelial growth factor (vegf) is essential to the developing vasculature of an embryo. Three rescue studies were designed to rescue MTBE-induced vascular lesions: pooled blood in the common cardinal vein (CCV), cranial hemorrhages (CH), and abnormal intersegmental vessels (ISV), and test the hypothesis that MTBE toxicity was HIF–Vegf dependent. First, zebrafish vegf-a over-expression via plasmid injection, resulted in significantly fewer CH and ISV lesions, 46 and 35% respectively, in embryos exposed to 10 mM MTBE. Then HIF degradation was inhibited in two ways. Chemical rescue by N-oxaloylglycine significantly reduced CCV and CH lesions by 30 and 32% in 10 mM exposed embryos, and ISV lesions were reduced 24% in 5 mM exposed zebrafish. Finally, a morpholino designed to knock-down ubiquitin associated von Hippel–Lindau protein, significantly reduced CCV lesions by 35% in 10 mM exposed embryos. In addition, expression of some angiogenesis related genes altered by MTBE exposure were rescued. These studies demonstrated that MTBE vascular toxicity is mediated by a down regulation of HIF–Vegf driven angiogenesis. The selective toxicity of MTBE toward developing vasculature makes it a potentially useful chemical in the designing of new drugs or in elucidating roles for specific angiogenic proteins in future studies of vascular development. - Highlights: • Global gene expression of MTBE exposed zebrafish suggested altered HIF1 signaling. • Over expression of zebrafish vegf-a rescues MTBE-induced

  15. Occult CSF flow disturbance of patients with Alzheimer type dementia and vascular dementia; Results from Iotrolan CT-cisternography

    Energy Technology Data Exchange (ETDEWEB)

    Kono, Kazuhiko; Sugita, Yasuko; Funaki, Chiaki (Nagoya Univ. (Japan). Faculty of Medicine) (and others)

    1994-04-01

    We report results of Iotrolan CT-cisternography on 41 demented patients (13 males and 28 females) to find 'occult normal pressure hydrocephalus'. These patients were suspected to have CSF flow disturbance from clinical symptoms and simple brain CT scan findings. Their average age, duration of dementia, and score of Hasegawa's dementia scale (HDS) were 76.2 years, 5.9 years, 9.5/32.5,respectively. Before performing CT-cisternography, clinical diagnosis for their dementia were vascular dementia in 18 patients. Alzheimer type dementia in 12, suspect of NPH in 5, and other diagnoses in 6. From the results of cisternography, we found 13 patients with CSF flow disturbance (contrast material remained in the ventricle more than 48 hours after injection), and 17 patients with normal CSF flow. The former showed lower scores of HDS, higher urinary incontinence scores and smaller areas of the interhemispheric fissure on CT scan than the latter. But the former showed no significant difference from the latter in the average age, duration of dementia and width of the ventricles. (author).

  16. Vascular smooth muscle cell glycocalyx mediates shear stress-induced contractile responses via a Rho kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway.

    Science.gov (United States)

    Kang, Hongyan; Liu, Jiajia; Sun, Anqiang; Liu, Xiao; Fan, Yubo; Deng, Xiaoyan

    2017-02-13

    The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3-4 days were exposed to a step increase (0 to 20 dyn/cm(2)) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction. The expressions of Rho kinase (ROCK) and its downstream signal molecules, the myosin-binding subunit of myosin phosphatase (MYPT) and the myosin light chain 2 (MLC2), were evaluated. Results showed that the exposure of HUVSMCs to shear stress for 30 min induced cell contraction significantly, which was accompanied by ROCK1 up-regulation, re-distribution, as well as MYPT1 and MLC activation. However, these shear induced phenomenon could be completely abolished by heparinase III or Y-27632 pre-treatment. These results indicate shear stress induced VSMC contraction was mediated by cell surface glycocalyx via a ROCK-MLC phosphatase (MLCP) pathway, providing evidence of the glycocalyx mechanotransduction in myogenic response.

  17. Regional cerebral blood flow before and after vascular surgery in patients with transient ischemic attacks with 133-xenon inhalation tomography

    DEFF Research Database (Denmark)

    Vorstrup, S; Hemmingsen, Ralf; Lindewald, H;

    1982-01-01

    with a spatial resolution of 1.7 cm. Based primarily on the clinical evidence and on the angiographical findings embolism was considered the pathogenetic factor in 10 cases, whereas chronic hemodynamic insufficiency rendered symptomatic by postural factors probably accounted for the symptoms in 4 patients....... Of the 14 patients, all studied days to weeks after the most recent TIA, four showed hypoperfused areas on the CBF-tomograms and with roughly the same location hypodense areas on CT-scanning, i.e. areas of complete infarction. However, an additional five patients showed reduction of CBF in areas...... with no abnormality on the CT-scan. The abnormal blood flow pattern was found to be unchanged after clinically successful reconstructive vascular surgery. This suggests the presence of irreversible ischemic tissue damage without gross emollition (incomplete infarction). It is concluded, that TIAs are often harmful...

  18. Evidence that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits angiogenesis by inducing vascular endothelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Pei-Lin, E-mail: pchen@dal.ca [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Easton, Alexander S., E-mail: alexander.easton@dal.ca [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Division of Neurosurgery, Department of Surgery, Dalhousie University, Halifax, Nova Scotia (Canada)

    2010-01-01

    Tumor necrosis factor (TNF) and its related ligands TNF-related apoptosis inducing ligand (TRAIL) and Fas ligand (FasL) play roles in the regulation of vascular responses, but their effect on the formation of new blood vessels (angiogenesis) is unclear. Therefore, we have examined the effects of these ligands on angiogenesis modeled with primary cultures of human umbilical vein endothelial cells (HUVEC). To examine angiogenesis in the context of the central nervous system, we have also modeled cerebral angiogenesis with the human brain endothelial cell line hCMEC/D3. Parameters studied were bromodeoxyuridine (BrdU) incorporation and cell number (MTT) assay (to assess endothelial proliferation), scratch assay (migration) and networks on Matrigel (tube formation). In our hands, neither TRAIL nor FasL (1, 10, and 100 ng/ml) had an effect on parameters of angiogenesis in the HUVEC model. In hCMEC/D3 cells by contrast, TRAIL inhibited all parameters (10-100 ng/ml, 24 h). This was due to apoptosis, since its action was blocked by the pan-caspase inhibitor zVADfmk (5 x 10{sup -5} mol/l) and TRAIL increased caspase-3 activity 1 h after application. However FasL (100 ng/ml) increased BrdU uptake without other effects. We conclude that TRAIL has different effects on in vitro angiogenesis depending on which model is used, but that FasL is generally ineffective when applied in vitro. The data suggest that TRAIL primarily influences angiogenesis by the induction of vascular endothelial apoptosis, leading to vessel regression.

  19. Shock-Induced Flows through Packed Beds: Transient Regimes

    CERN Document Server

    Shtemler, Yuri M; Britan, Alex

    2006-01-01

    The early stage of the transient regimes in the shock-induced flows within solid-packed beds are investigated in the linear longwave and high-frequency approximation. The transient resistance law is refined as the Duhameltime integral that follows from the general concept of dynamic tortuosity and compressibility of the packed beds. A closed-form solution is expected to describe accurately the early stage of the transient regime flow and is in qualitative agreement with available experimental data.

  20. Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia-Induced Neovascularization: The Role of Dipeptidyl Peptidase-4/Glucagon-Like Peptide-1-Adiponectin Axis.

    Science.gov (United States)

    Piao, Limei; Zhao, Guangxian; Zhu, Enbo; Inoue, Aiko; Shibata, Rei; Lei, Yanna; Hu, Lina; Yu, Chenglin; Yang, Guang; Wu, Hongxian; Xu, Wenhu; Okumura, Kenji; Ouchi, Noriyuki; Murohara, Toyoaki; Kuzuya, Masafumi; Cheng, Xian Wu

    2017-09-28

    Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon-like peptide-1 (GLP-1) metabolism, we investigated the role of DPP4/GLP-1 axis in vascular senescence and ischemia-induced neovascularization in mice under chronic stress, with a special focus on adiponectin -mediated peroxisome proliferator activated receptor-γ/its co-activator 1α (PGC-1α) activation. Seven-week-old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood-flow ratio throughout the follow-up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle DPP4 and decreased levels of GLP-1 and adiponectin in plasma and phospho-AMP-activated protein kinase α (p-AMPKα), vascular endothelial growth factor, peroxisome proliferator activated receptor-γ, PGC-1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial CD31(+)/c-Kit(+) progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting. DPP4 inhibition and GLP-1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion. These results indicate that the DPP4/GLP-1-adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  1. Possible vasculoprotective role of linagliptin against sodium arsenite-induced vascular endothelial dysfunction.

    Science.gov (United States)

    Jyoti, Uma; Kansal, Sunil Kumar; Kumar, Puneet; Goyal, Sandeep

    2016-02-01

    Vascular endothelial dysfunction (VED) interrupts the integrity and function of endothelial lining through enhanced markers of oxidative stress and decrease endothelial nitric oxide synthase (eNOS) expression. The main aim of the present study has been designed to investigate the possible vasculoprotective role of linagliptin against sodium arsenite-induced VED. Sodium arsenite (1.5 mg/kg, i.p., 2 weeks) abrogated the acetylcholine-induced, endothelium-dependent vasorelaxation by depicting the decrease in serum nitrite/nitrate concentration, reduced glutathione level, and simultaneously enhance the thiobarbituric acid reactive substances (TBARS) level, superoxide level, and tumor necrosis factor-alpha. These elevated markers interrupt the integrity of endothelial lining of thoracic aorta which was assessed histologically. The study elicits dose dependent effect of linagliptin (1.5 mg/kg, i.p. and 3 mg/kg, i.p.) or atorvastatin (30 mg/kg, p.o.) treatment, improved the endothelium-dependent independent relaxation, improve the integrity of endothelium lining which was assessed histologically by enhancing the serum nitrite/nitrate level, reduced glutathione level and simultaneously decreasing the TBARS level, superoxide anion level and tumor necrosis factor-alpha (TNF-α) level. L-NAME (25 mg/kg, i.p.), eNOS inhibitor, abrogated the ameliorative potential of linagliptin. However, the ameliorative potential of linagliptin has been enhanced by l-arginine (200 mg/kg, i.p.) which elicits that ameliorative potential of linagliptin was through eNOS signaling cascade and it may be concluded that linagliptin 3 mg/kg, i.p. has more significantly activated the eNOS and decreased the oxidative markers than linagliptin 1.5 mg/kg, i.p. and prevented sodium arsenite-induced VED.

  2. Protective vascular and cardiac effects of inducible nitric oxide synthase in mice with hyperhomocysteinemia.

    Directory of Open Access Journals (Sweden)

    Sanjana Dayal

    Full Text Available Diet-induced hyperhomocysteinemia produces endothelial and cardiac dysfunction and promotes thrombosis through a mechanism proposed to involve oxidative stress. Inducible nitric oxide synthase (iNOS is upregulated in hyperhomocysteinemia and can generate superoxide. We therefore tested the hypothesis that iNOS mediates the adverse oxidative, vascular, thrombotic, and cardiac effects of hyperhomocysteinemia. Mice deficient in iNOS (Nos2-/- and their wild-type (Nos2+/+ littermates were fed a high methionine/low folate (HM/LF diet to induce mild hyperhomocysteinemia, with a 2-fold increase in plasma total homocysteine (P<0.001 vs. control diet. Hyperhomocysteinemic Nos2+/+ mice exhibited endothelial dysfunction in cerebral arterioles, with impaired dilatation to acetylcholine but not nitroprusside, and enhanced susceptibility to carotid artery thrombosis, with shortened times to occlusion following photochemical injury (P<0.05 vs. control diet. Nos2-/- mice had decreased rather than increased dilatation responses to acetylcholine (P<0.05 vs. Nos2+/+ mice. Nos2-/- mice fed control diet also exhibited shortened times to thrombotic occlusion (P<0.05 vs. Nos2+/+ mice, and iNOS deficiency failed to protect from endothelial dysfunction or accelerated thrombosis in mice with hyperhomocysteinemia. Deficiency of iNOS did not alter myocardial infarct size in mice fed the control diet but significantly increased infarct size and cardiac superoxide production in mice fed the HM/LF diet (P<0.05 vs. Nos2+/+ mice. These findings suggest that endogenous iNOS protects from, rather than exacerbates, endothelial dysfunction, thrombosis, and hyperhomocysteinemia-associated myocardial ischemia-reperfusion injury. In the setting of mild hyperhomocysteinemia, iNOS functions to blunt cardiac oxidative stress rather than functioning as a source of superoxide.

  3. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Energy Technology Data Exchange (ETDEWEB)

    Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: sarasate2222@gmail.com [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2015-05-01

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

  4. Experimental diabetes induces structural, inflammatory and vascular changes of Achilles tendons.

    Directory of Open Access Journals (Sweden)

    Rodrigo R de Oliveira

    Full Text Available This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS and nitrate and nitrite level. The Achilles tendon thickness (µm/100g of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98 vessels/field when compared to the control group 0.89 (1.68 vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18 vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99 vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.

  5. Barnidipine ameliorates the vascular and renal injury in L-NAME-induced hypertensive rats.

    Science.gov (United States)

    Alp Yildirim, F Ilkay; Eker Kizilay, Deniz; Ergin, Bülent; Balci Ekmekçi, Özlem; Topal, Gökçe; Kucur, Mine; Demirci Tansel, Cihan; Uydeş Doğan, B Sönmez

    2015-10-05

    The present study was aimed to investigate the influence of Barnidipine treatment on early stage hypertension by determining the function and morphology of the mesenteric and renal arteries as well as the kidney in N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced hypertensive rats. Barnidipine (3 mg/kg/day p.o) was applied to rats after 2 weeks of L-NAME (60 mg/kg/day) administration, and continued for the next 3 weeks concomitantly with L-NAME. The systolic blood pressure (SBP) of rats was determined to decrease significantly in Barnidipine treated hypertensive group when compared to that of rats received L-NAME alone. Myograph studies demonstrated that the contractile reactivity to noradrenaline were significantly reduced in both of the resistance arteries while endothelium-dependent relaxations to acethylcholine were significantly diminished particularly in the mesenteric arteries of L-NAME-induced hypertensive rats. The impaired contractile and endothelial responses were completely restored by concomitant treatment of Barnidipine with L-NAME. Histopathological examinations verified structural alterations in the arteries as well as the kidney. Moreover, a decrease in endothelial nitric oxide synthase (eNOS) expression was presented both in the arteries and kidney of hypertensive rats which were increased following Barnidipine treatment. Elevated plasma levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were also reduced in Barnidipine treated hypertensive rats. In conclusion, besides to its efficacy in reducing the elevated SBP, amelioration of vascular function, modulation of arterial and renal eNOS expressions as well as reduction of the plasma levels of oxidative and inflammatory biomarkers are possible supportive mechanisms mediating the favorable implications of Barnidipine in L-NAME-induced hypertension model.

  6. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    Energy Technology Data Exchange (ETDEWEB)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. (Medical Univ. of South Carolina, Charleston (USA))

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  7. Vascular dysfunction induced in offspring by maternal dietary fat involves altered arterial polyunsaturated fatty acid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Christopher J Kelsall

    Full Text Available Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w or 21%(w/w fat enriched in either 18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Δ6 and Δ5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Δ6 and Δ5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG -394 bp 5' to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05. This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and

  8. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Ju Huo; Ying Zhao; Yu Tian

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories.Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model.The fitting curves for each factor were obtained using Matlab software.Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors.Our results demonstrated that vascular cognitive impairment involves multiple factors.These factors include excitatory amino acid toxicity and nitric oxide toxicity.These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  9. Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study

    Directory of Open Access Journals (Sweden)

    Tolón Rosa M

    2011-01-01

    Full Text Available Abstract Background The phytocannabinoid cannabidiol (CBD exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS. Methods Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR. Results CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD. Conclusions These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid.

  10. Disparity in regional cerebral blood flow during electrically induced seizure

    DEFF Research Database (Denmark)

    Sestoft, D; Meden, P; Hemmingsen, R

    1993-01-01

    This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized on electroencepha......This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized...... electroencephalography-verified generalized seizures....

  11. Vibration induced flow in hoppers: DEM 2D polygon model

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A two-dimensional discrete element model (DEM) simulation of cohesive polygonal particles has been developed to assess the benefit of point source vibration to induce flow in wedge-shaped hoppers. The particle-particle interaction model used is based on a multi-contact principle.The first part of the study investigated particle discharge under gravity without vibration to determine the critical orifice size (Be) to just sustain flow as a function of particle shape. It is shown that polygonal-shaped particles need a larger orifice than circular particles. It is also shown that Be decreases as the number of particle vertices increases. Addition of circular particles promotes flow of polygons in a linear manner.The second part of the study showed that vibration could enhance flow, effectively reducing Be. The model demonstrated the importance of vibrator location (height), consistent with previous continuum model results, and vibration amplitude in enhancing flow.

  12. Fish oil blunted nicotine-induced vascular endothelial abnormalities possibly via activation of PPARγ-eNOS-NO signals.

    Science.gov (United States)

    Taneja, Gaurav; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-06-01

    Nicotine exposure is associated with an induction of vascular endothelial dysfunction (VED), a hallmark of various cardiovascular disorders. The present study investigated the effect of fish oil in nicotine-induced experimental VED. VED was assessed by employing isolated aortic ring preparation, estimating aortic and serum nitrite/nitrate, aortic superoxide anion generation, and serum TBARS, and carrying out electron microscopic and histological studies of thoracic aorta. Nicotine (2 mg/kg/day, i.p., 4 weeks) administration produced VED in rats by attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentration, impairing endothelial integrity, and inducing vascular oxidative stress. Treatment with fish oil (2 mL/kg/day p.o., 4 weeks) markedly prevented nicotine-induced endothelial functional and structural abnormalities and oxidative stress. However, administration of GW9662, a selective inhibitor of PPARγ, to a significant degree attenuated fish oil-associated anti-oxidant action and vascular endothelial functional and structural improvements. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase (NOS), markedly attenuated fish oil-induced improvement in endothelium-dependent relaxation in the aorta of nicotine-administered rats. Nicotine administration altered the lipid profile by increasing serum total cholesterol, which was significantly prevented by fish oil treatment. The vascular protective potential of fish oil in preventing nicotine-induced VED may pertain to its additional properties (besides its lipid-lowering effect) such as activation of PPARγ and subsequent possible activation of endothelial NOS and generation of nitric oxide, and consequent reduction in oxidative stress.

  13. Correlation of isolability of the oak wilt pathogen with leaf wilt and vascular water flow resistance

    Science.gov (United States)

    Garold F. Gregory

    1971-01-01

    Isolations and water flow-rate measurements made on short stem sections of young red oak seedlings inoculated with the oak wilt pathogen, Ceratocystis fagacearum, about 1 to 2 inches above the soil line, revealed that the oak wilt pathogen was isolable first near the inoculation site. As time after inoculation increased, the pathogen was isolated...

  14. Intraoperative vascular anatomy, arterial blood flow velocity, and microcirculation in unilateral and bilateral cleft lip repair

    NARCIS (Netherlands)

    Mueller, A.A.; Schumann, D.; Reddy, R.R.; Schwenzer-Zimmerer, K.; Mueller-Gerbl, M.; Zeilhofer, H.F.; Sailer, H.F.; Reddy, S.G.

    2012-01-01

    BACKGROUND: Cleft lip repair aims to normalize the disturbed anatomy and function. The authors determined whether normalization of blood circulation is achieved. METHODS: The authors measured the microcirculatory flow, oxygen saturation, and hemoglobin level in the lip and nose of controls (n = 22)

  15. Medium-induced color flow softens hadronization

    CERN Document Server

    Beraudo, A; Wiedemann, U A

    2012-01-01

    Medium-induced parton energy loss, resulting from gluon exchanges between the QCD matter and partonic projectiles, is expected to underly the strong suppression of jets and high-$p_T$ hadron spectra observed in ultra-relativistic heavy ion collisions. Here, we present the first color-differential calculation of parton energy loss. We find that color exchange between medium and projectile enhances the invariant mass of energetic color singlet clusters in the parton shower by a parametrically large factor proportional to the square root of the projectile energy. This effect is seen in more than half of the most energetic color-singlet fragments of medium-modified parton branchings. Applying a standard cluster hadronization model, we find that it leads to a characteristic additional softening of hadronic spectra. A fair description of the nuclear modification factor measured at the LHC may then be obtained for relatively low momentum transfers from the medium.

  16. Possible involvement of phospholipase D and protein kinase C in vascular growth induced by elevated glucose concentration.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Horio, T; Yoshikawa, J

    1996-08-01

    Hyperglycemia is believed to be a major cause of diabetic vascular complications. To elucidate the effect of hyperglycemia on vascular response, we studied hyperproliferation, hypertrophy, and the natriuretic peptide response of vascular smooth muscle cells under high-glucose conditions. We observed that cells cultured in high glucose (22.2 mmol/L) showed hyper-proliferation and hypertrophy and that natriuretic peptide receptor responses were suppressed compared with cells cultured in normal glucose (5.6 mmol/L). We also examined phospholipase D and protein kinase C activities and found that in high-glucose conditions such activities are higher than in cells cultured in normal glucose. The activation of phospholipase D was not prevented by coincubation with 1 mumol/L protein kinase C(19-36), a specific protein kinase C inhibitor, but the activation of protein kinase C was. Protein kinase C(19-36) also markedly attenuated vascular hyperproliferation and hypertrophy as well as glucose-induced suppression of natriuretic peptide receptor response. These results show that hyperglycemia may be linked to vascular hyperproliferation, hypertrophy, and a suppressed natriuretic peptide receptor response, which are caused by increased phospholipase D and protein kinase C activities.

  17. Angiotensin-(1-7) regulates Angiotensin II-induced VCAM-1 expression on vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Feng [Department of Cardiology, Peking University People' s Hospital, Beijing (China); William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (United Kingdom); Ren, Jingyi [Department of Cardiology, Peking University People' s Hospital, Beijing (China); Chan, Kenneth [William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (United Kingdom); Chen, Hong, E-mail: chenhongbj@medmail.com.cn [Department of Cardiology, Peking University People' s Hospital, Beijing (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer We for the first time found that Ang-(1-7) inhibits Ang II-induced VCAM-1 expression. Black-Right-Pointing-Pointer The inhibitory effect of Ang-(1-7) on VCAM-1 is mediated by MAS receptor. Black-Right-Pointing-Pointer The effect of Ang-(1-7) is due to the suppression of NF-kappaB translocation. -- Abstract: Angiotensin II (Ang II) and Angiotensin-(1-7) (Ang-(1-7)) are key effector peptides in the renin-angiotensin system. Increased circulatory Ang II level is associated with the development of hypertension and atherosclerosis, whereas Ang-(1-7) is a counter-regulatory mediator of Ang II which appears to be protective against cardiovascular disease. However, whether Ang-(1-7) regulates the action of Ang II on vascular endothelial cells (EC) remains unclear. We investigated the effects of Ang II and Ang-(1-7) in the context of atherogenesis, specifically endothelial cell VCAM-1 expression that is implicated in early plaque formation. The results show that Ang II increased VCAM-1 mRNA expression and protein displayed on EC surface, while Ang-(1-7) alone exerted no effects. However, Ang-(1-7) significantly suppressed Ang II-induced VCAM-1 expression. Ang-(1-7) also inhibited the Ang II-induced VCAM-1 promoter activity driven by transcription factor NF-KappaB. Furthermore, immunofluorescence assay and ELISA showed that Ang II facilitated the nuclear translocation of NF-kappaB in ECs, and this was attenuated by the presence of Ang-(1-7). The inhibitory effects of Ang-(1-7) on Ang II-induced VCAM-1 promoter activity and NF-kappaB nuclear translocation were all reversed by the competitive antagonist of Ang-(1-7) at the Mas receptor. Our results suggest that Ang-(1-7) mediates its affects on ECs through the Mas receptor, and negatively regulates Ang II-induced VCAM-1 expression by attenuating nuclear translocation of NF-kappaB.

  18. Modelling ultrasound-induced mild hyperthermia of hyperplasia in vascular grafts

    Directory of Open Access Journals (Sweden)

    Cheung Alfred K

    2011-11-01

    Full Text Available Abstract Background Expanded polytetrafluoroethylene (ePTFE vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood. Methods Ultrasound beams from two transducers (1.5 and 3.2 MHz were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL® Multiphysics heat transfer model. 50°C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13°C temperature rise from 37°C in the ePTFE. Results Simulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native

  19. Changes in vascular and transpiration flows affect the seasonal and daily growth of kiwifruit (Actinidia deliciosa) berry

    Science.gov (United States)

    Morandi, Brunella; Manfrini, Luigi; Losciale, Pasquale; Zibordi, Marco; Corelli Grappadelli, Luca

    2010-01-01

    Background and Aims The kiwifruit berry is characterized by an early stage of rapid growth, followed by a relatively long stage of slow increase in size. Vascular and transpiration flows are the main processes through which water and carbon enter/exit the fruit, determining the daily and seasonal changes in fruit size. This work investigates the biophysical mechanisms underpinning the change in fruit growth rate during the season. Methods The daily patterns of phloem, xylem and transpiration in/outflows have been determined at several stages of kiwifruit development, during two seasons. The different flows were quantified by comparing the diurnal patterns of diameter change of fruit, which were then girdled and subsequently detached while measurements continued. The diurnal courses of leaf and stem water potential and of fruit pressure potential were also monitored at different times during the season. Key Results Xylem and transpiration flows were high during the first period of rapid volume growth and sharply decreased with fruit development. Specific phloem import was lower and gradually decreased during the season, whereas it remained constant at whole-fruit level, in accordance with fruit dry matter gain. On a daily basis, transpiration always responded to vapour pressure deficit and contributed to the daily reduction of fruit hydrostatic pressure. Xylem flow was positively related to stem-to-fruit pressure potential gradient during the first but not the last part of the season, when xylem conductivity appeared to be reduced. Conclusions The fruit growth model adopted by this species changes during the season due to anatomical modifications in the fruit features. PMID:20382641

  20. Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway.

    Science.gov (United States)

    Nallasamy, Palanisamy; Si, Hongwei; Babu, Pon Velayutham Anandh; Pan, Dengke; Fu, Yu; Brooke, Elizabeth A S; Shah, Halley; Zhen, Wei; Zhu, Hong; Liu, Dongmin; Li, Yunbo; Jia, Zhenquan

    2014-08-01

    Sulforaphane, a naturally occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as 0.5 μM significantly inhibited tumor necrosis factor-α (TNF-α)-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of sulforaphane also significantly suppressed TNF-α-induced production of monocyte chemotactic protein-1 and adhesion molecules including soluble vascular adhesion molecule-1 and soluble E-selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, sulforaphane inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, Inhibitor of NF-κB alpha (IκBα) degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit inflammation by suppressing NF-κB signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization, as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that sulforaphane treatment also reduced vascular adhesion molecule-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti

  1. Inhibition of nitric oxide synthases abrogates pregnancy-induced uterine vascular expansive remodeling.

    Science.gov (United States)

    Osol, George; Barron, Carolyn; Gokina, Natalia; Mandala, Maurizio

    2009-01-01

    It was the aim of this study to test the hypothesis that hypertension and/or inhibition of nitric oxide (NO) synthases alters uterine vascular remodeling during pregnancy. Using a model of hypertension (NO synthase inhibition with L-NAME) in nonpregnant and pregnant rats, comparisons were made with age-matched controls, as well as with animals receiving hydralazine along with L-NAME to maintain normotension in the presence of NO synthase inhibition. Circumferential and axial remodeling of large (main uterine, MUA) and small (premyometrial radial) arteries were quantified and compared. L-NAME treatment prevented expansive circumferential remodeling of the MUA; cotreatment with hydralazine was without effect. Circumferential remodeling of smaller premyometrial radial arteries was also significantly attenuated in hypertensive pregnant animals, while premyometrial radial arteries from rats receiving hydralazine with L-NAME were of intermediate diameter. Neither hypertension nor NO synthase inhibition had any effect on the substantial (200-300%) axial growth of MUA or premyometrial radial arteries. NO plays a major role in facilitating pregnancy-induced expansive remodeling in the uterine circulation, particularly in larger arteries. Some beneficial effects of hydralazine on expansive circumferential remodeling were noted in smaller radial vessels, and these may be linked to its prevention of systemic hypertension and/or to local effects on the arterial wall. Neither NO synthase inhibition nor hypertension had any effect on arterial longitudinal growth.

  2. D609 induces vascular endothelial cells and marrow stromal cells differentiation into neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Nan WANG; Chun-qing DU; Shao-shan WANG; Kun XIE; Shang-li ZHANG; Jun-ying MIAO

    2004-01-01

    AIM: To investigate the effect of tricyclodecane-9-yl-xanthogenate (D609) on cell differentiation in vascular endothelial cells (VECs) and marrow stromal cells (MSCs). METHODS: Morphological changes were observed under phase contrast microscope. Electron microscope and immunostaining were used for VECs identification. The expressions of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. RESULTS: After 6 h of induction with D609, some VECs showed morphological changes characteristic of neurones. 9 h later, more VECs became neuron-like cells. About 30.8 % of VECs displayed positive NSE (P<0.01), while the expression of GFAP was negative. When MSCs were exposed to D609, the cells displayed neuronal morphologies, such as pyramidal cell bodies and processes formed extensive networks at 3 h. 6 h later, almost all of the cells exhibited a typical neuronal appearance, and 85.6 % of MSCs displayed intensive positive NSE, but GFAP did not express. CONCLUSION: D609 induces VECs and MSCs differentiation into neuron-like cells.

  3. Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

    Institute of Scientific and Technical Information of China (English)

    Tomoyuki Okuda; Takeshi Azuma; Masahiro Ohtani; Ryuho Masaki; Yoshiyuki Ito; Yukinao Yamazaki; Shigeji Ito; Masaru Kuriyama

    2005-01-01

    AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic favors such as hypoxia-inducible factor 1 alpha (HIF-1alpha and vascular endothelial growth factor (VEGF).METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after theoccurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF.RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry.HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis.CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

  4. Microparticle-Induced Activation of the Vascular Endothelium Requires Caveolin-1/Caveolae.

    Directory of Open Access Journals (Sweden)

    Allison M Andrews

    Full Text Available Microparticles (MPs are small membrane fragments shed from normal as well as activated, apoptotic or injured cells. Emerging evidence implicates MPs as a causal and/or contributing factor in altering normal vascular cell phenotype through initiation of proinflammatory signal transduction events and paracrine delivery of proteins, mRNA and miRNA. However, little is known regarding the mechanism by which MPs influence these events. Caveolae are important membrane microdomains that function as centers of signal transduction and endocytosis. Here, we tested the concept that the MP-induced pro-inflammatory phenotype shift in endothelial cells (ECs depends on caveolae. Consistent with previous reports, MP challenge activated ECs as evidenced by upregulation of intracellular adhesion molecule-1 (ICAM-1 expression. ICAM-1 upregulation was mediated by activation of NF-κB, Poly [ADP-ribose] polymerase 1 (PARP-1 and the epidermal growth factor receptor (EGFR. This response was absent in ECs lacking caveolin-1/caveolae. To test whether caveolae-mediated endocytosis, a dynamin-2 dependent process, is a feature of the proinflammatory response, EC's were pretreated with the dynamin-2 inhibitor dynasore. Similar to observations in cells lacking caveolin-1, inhibition of endocytosis significantly attenuated MPs effects including, EGFR phosphorylation, activation of NF-κB and upregulation of ICAM-1 expression. Thus, our results indicate that caveolae play a role in mediating the pro-inflammatory signaling pathways which lead to EC activation in response to MPs.

  5. Insulin induces PKC-dependent proliferation of mesenteric vascular smooth muscle cells from hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    Xukai WANG; Yan WANG; Chenming YANG; Ying WAN; Xianwen JI

    2006-01-01

    Background and objectives Proliferation of human vascular smooth muscle cells (VSMCs) induced by hyperinsulinemia is a very common clinical pathology. Extensive research has focused on PKC (Protein kinase C)-MAPK (mitogen-activated protein kinase)intracellular signal transduction and the phenotypic modulation accompanied by reorganization of intracellular F-actins in VSMCs.Methods DNA synthesis, signaling of ERK1/2 MAPKs, and changes in α-smooth muscle (SM) actin and F-actin were studied in hypertensive and normotensive human arterial VSMCs exposed to insulin and PMA with and without the PKC inhibitor, GF109203X.Results Differences among cell types in MAPK signaling, α-SM actin, and F-actin isoforms in VSMCs harvested from the arteries of patients with essential hypertension (EH) and normotension (NT) were identified in response to insulin treatment. Proliferation and activation of MAPK were more pronounced in EH VSMCs than in NEH VSMCs. Insulin exposure decreased expression of α-SM actin and was accompanied by rearrangement of intracellular F-actins in VSMCs, especially in the EH group. These effects were reversed by treatment with the PKC inhibitor. Conclusions Human mesenteric VSMCs of EH and NT patients differed in proliferation, MAPK signaling, and degree of changes in α-SM actin and F-actin isoforms immediately following insulin exposure in vitro.

  6. The decrease of serum vascular endothelial growth factor concentration in patients with pregnancy induced hypertension

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objectives:To detect the concentration of serum vascular endothelial growth factor (VEGF) in patients with pregnancy induced hypertension (PIH) as well as to explore the role of VEGF in the pathogenesis of PIH.Methods:Serum VEGF concentrations in 23 healthy nonpregnant women (normal group),30 normal pregnant women (control group) and 37 women with PIH (PIH group) were measured by sandwich enzyme-linked immunoadsorbent assay (ELISA).Results:Serum concentrations of VEGF in control group were significantly higher (149.39±27.15ng/L) than those in normal group (11.98±3.99ng/L) (P<0.001),peaking in the second trimester of pregnancy (183.84±49.02ng/L) and decreasing in the third trimester (118.37±34.29ng/L).Serum VEGF concentrations (64.45±24.33ng/L) in PIH group were significantly lower than those in normal late pregnancy women of control group (118.37±34.29ng/L) (P<0.01).There was a trend that serum VEGF concentrations in PIH group decreased with the severity of PIH (P<0.05).Conclusion:The serum VEGF concentration in PIH women are significantly decreased,which suggests that VEGF may play an important role in the pathogenic mechanism of PIH.

  7. Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2015-07-01

    Full Text Available Background/Aim: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6-methylanthraquinone, which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. Methods: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg or saline (control. Emodin (4 mg/kg was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Results: Emodin significantly prevented the increase of leukocyte (n=8, Pin vivo prothrombotic effect of DEP in pial arterioles (n=6, Pin vitro in whole blood (n=4-5, PConclusion: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution.

  8. Disturbance of copper homeostasis is a mechanism for homocysteine-induced vascular endothelial cell injury.

    Directory of Open Access Journals (Sweden)

    Daoyin Dong

    Full Text Available Elevation of serum homocysteine (Hcy levels is a risk factor for cardiovascular diseases. Previous studies suggested that Hcy interferes with copper (Cu metabolism in vascular endothelial cells. The present study was undertaken to test the hypothesis that Hcy-induced disturbance of Cu homeostasis leads to endothelial cell injury. Exposure of human umbilical vein endothelial cells (HUVECs to concentrations of Hcy at 0.01, 0.1 or 1 mM resulted in a concentration-dependent decrease in cell viability and an increase in necrotic cell death. Pretreatment of the cells with a final concentration of 5 µM Cu in cultures prevented the effects of Hcy. Hcy decreased intracellular Cu concentrations. HPLC-ICP-MS analysis revealed that Hcy caused alterations in the distribution of intracellular Cu; more Cu was redistributed to low molecular weight fractions. ESI-Q-TOF detected the formation of Cu-Hcy complexes. Hcy also decreased the protein levels of Cu chaperone COX17, which was accompanied by a decrease in the activity of cytochrome c oxidase (CCO and a collapse of mitochondrial membrane potential. These effects of Hcy were all preventable by Cu pretreatment. The study thus demonstrated that Hcy disturbs Cu homeostasis and limits the availability of Cu to critical molecules such as COX17 and CCO, leading to mitochondrial dysfunction and endothelial cell injury.

  9. Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

    DEFF Research Database (Denmark)

    Bartels, E D; Bang, C A; Nielsen, L B

    2009-01-01

    BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development...... and soluble vascular cell adhesion molecule-1 (sVCAM-1) in both wild-type and apoB transgenic mice. In wild-type mice, plasma very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were unaffected by fat-feeding. ApoB transgenic mice had mildly elevated plasma LDL...... and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early...

  10. Growth factors induce monocyte binding to vascular smooth muscle cells: implications for monocyte retention in atherosclerosis.

    Science.gov (United States)

    Cai, Qiangjun; Lanting, Linda; Natarajan, Rama

    2004-09-01

    Adhesive interactions between monocytes and vascular smooth muscle cells (VSMC) may contribute to subendothelial monocyte-macrophage retention in atherosclerosis. We investigated the effects of angiotensin II (ANG II) and platelet-derived growth factor (PDGF)-BB on VSMC-monocyte interactions. Treatment of human aortic VSMC (HVSMC) with ANG II or PDGF-BB significantly increased binding to human monocytic THP-1 cells and to peripheral blood monocytes. This was inhibited by antibodies to monocyte beta(1)- and beta(2)-integrins. The binding was also attenuated by blocking VSMC arachidonic acid (AA) metabolism by inhibitors of 12/15-lipoxygenase (12/15-LO) or cyclooxygenase-2 (COX-2). Conversely, binding was enhanced by overexpression of 12/15-LO or COX-2. Direct treatment of HVSMC with AA or its metabolites also increased binding. Furthermore, VSMC derived from 12/15-LO knockout mice displayed reduced binding to mouse monocytic cells relative to genetic control mice. Using specific signal transduction inhibitors, we demonstrated the involvement of Src, phosphoinositide 3-kinase, and MAPKs in ANG II- or PDGF-BB-induced binding. Interestingly, after coculture with HVSMC, THP-1 cell surface expression of the scavenger receptor CD36 was increased. These results show for the first time that growth factors may play additional roles in atherosclerosis by increasing monocyte binding to VSMC via AA metabolism and key signaling pathways. This can lead to monocyte subendothelial retention, CD36 expression, and foam cell formation.

  11. Endoplasmic reticulum stress induced by Thapsigargin in vascular smooth muscle cells of rat coronary artery

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-yan; DENG Chun-yu; JIANG Li

    2016-01-01

    AIM:To establish the endoplasmic reticulum stress ( ERS) cell model in vascular smooth muscle cells ( VSMCs) of Sprague-Dawley (SD) rats.METHODS:Under sterile condition, the coronary arteries were isolated from SD rats .The primary VSMCs were cultured by tissue-sticking method , and observed the basic morphological characteristics under optical microscope .The marker proteins of VSMCs including α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain ( SM-MHC) were identified by immuno-fluorescence technique .VSMCs were treated with thapsigargin (0.5, 1 and 2 μmol/L) for 24 h, and the expression levels of binding immunoglobulin protein (BiP) and C/EBP homologus protein (CHOP), the marker molecules of ERS, were detected using Western blotting.RESULTS:VSMCs climbed out from coronary artery tissues after about six days , and the cells had a nice state and formed the VSMC-like typical "peak valley".The results of immunofluorescence technique show that the marker proteins of VSMCs ,α-SMA and SM-MHC were expressed significantly .The results of Western blotting show that the protein expression levels of BiP and CHOP were increased by thapsigargin in a dose-dependent manner .CONCLUSION:VSMCs can be successfully cultured by tissue-sticking method and built the ERS model induced by thapsigargin .

  12. Tissue differences in vascular permeability induced by leukotriene B4 and prostaglandin E2 in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Stenson, W.F.; Chang, K.; Williamson, J.R.

    1986-07-01

    The activity of synthetic LTB4 and PGE2, in increasing vascular permeability was tested simultaneously in seventeen different organs in the rat. Rats were injected in the aortic arch through a cannula in the carotid artery with /sup 125/I-albumin, /sup 51/Cr-erythrocytes, and /sup 57/Co-EDTA. The rats were then injected through the carotid artery cannula with LTB4, PGE2 or a combination of LTB4 and PGE2. Eight minutes later the rats were killed and the activity of /sup 125/I, /sup 51/Cr, and /sup 57/Co measured in different organs. Changes in vascular permeability were inferred from changes in the ratios of the isotope activities. LTB4 (15 micrograms/kg) induced enhanced permeability in caecum, small bowel, skin, fat pad, stomach, pancreas, and aorta, but not in the heart, brain, colon, testes, diaphragm, forelimb, cremaster muscle, lung, kidney or eye. A lower dose of LTB4, 3 micrograms/kg, enhanced vascular permeability in caecum, small bowel, skin, stomach, and aorta. PGE2 (1 microgram/kg) enhanced vascular permeability only in the caecum. A combination of LTB4 (3 micrograms/kg) and PGE2 (1 microgram/kg) was more potent than either alone. Rats depleted of neutrophils with anti-neutrophil serum were less sensitive to LTB4 than intact rats. These findings suggest that the vasculatures of different tissues in the rat vary markedly in their susceptibility to LTB4 induced increases in permeability.

  13. Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

    Directory of Open Access Journals (Sweden)

    Li Jing

    2011-11-01

    Full Text Available The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2 inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY rats, spontaneously hypertensive rats (SHR and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

  14. An evaluation of a hubless inducer and a full flow hydraulic turbine driven inducer boost pump

    Science.gov (United States)

    Lindley, B. K.; Martinson, A. R.

    1971-01-01

    The purpose of the study was to compare the performance of several configurations of hubless inducers with a hydrodynamically similar conventional inducer and to demonstrate the performance of a full flow hydraulic turbine driven inducer boost pump using these inducers. A boost pump of this type consists of an inducer connected to a hydraulic turbine with a high speed rotor located in between. All the flow passes through the inducer, rotor, and hydraulic turbine, then into the main pump. The rotor, which is attached to the main pump shaft, provides the input power to drive the hydraulic turbine which, in turn, drives the inducer. The inducer, rotating at a lower speed, develops the necessary head to prevent rotor cavitation. The rotor speed is consistent with present main engine liquid hydrogen pump designs and the overall boost pump head rise is sufficient to provide adequate main pump suction head. This system would have the potential for operating at lower liquid hydrogen tank pressures.

  15. Vascular centerline extraction in 3D MR angiograms for phase contrast MRI blood flow measurement

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez Hoyos, M. [CREATIS, CNRS 5515 et INSERM U630 Research Unit, INSA de Lyon, 69 - Villeurbanne (France); Universidad de los Andes, Bogota (Colombia). Grupo Imagine, Grupo de Ingenieria Biomedica; Orlowski, P.; Piatkowska-Janko, E.; Bogorodzki, P. [Warsaw Univ. of Tech. (Poland). ZEJM-BINSK, Inst. of Radioelectronics; Orkisz, M. [CREATIS, CNRS 5515 et INSERM U630 Research Unit, INSA de Lyon, 69 - Villeurbanne (France)

    2006-03-15

    The accuracy of 2D phase contrast (PC) magnetic resonance angiography (MRA) depends on the alignment between the vessels and the imaging plane. PC MRA imaging of blood flow is challenging when the flow in several vessels is to be evaluated with one acquisition. For this purpose, semi-automatic determination of the plane most perpendicular to several vessels is proposed based on centerlines extracted from 3D MRA. Arterial centerlines are extracted from 3D MRA based on iterative estimation-prediction, multi-scale analysis of image moments, and a second-order shape model. The optimal plane is determined by minimizing misalignment between its normal vector and the centerlines' tangent vectors. The method was evaluated on a phantom and on 35 patients, by seeking the optimal plane for cerebral blood flow quantification simultaneously in internal carotids and vertebral arteries. In the phantom, difference of orientation and of height between known and calculated planes was 1.2 and 2.5 mm, respectively. In the patients, all but one centerline were correctly extracted and the misalignment of the plane was within 12 per artery. Semi-automatic centerline extraction simplifies and automates determination of the plane orthogonal to one vessel, thereby permitting automatic simultaneous minimization of the misalignment with several vessels in PC MRA. (orig.)

  16. Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease.

    Science.gov (United States)

    Grau-Monge, Cristina; Delcroix, Gaëtan J-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F; Armour, Maxime R; Montero, Ramon B; Schiller, Paul C; Andreopoulos, Fotios M; D'Ippolito, Gianluca

    2017-02-17

    Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of two layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration.

  17. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  18. Assessment of Serum Vascular Endothelial Growth Factor Levels in Pregnancy-Induced Hypertension Patients

    Science.gov (United States)

    Tandon, Vibha; Hiwale, Swati; Amle, Dnyanesh; Nagaria, Tripti

    2017-01-01

    Objective. The objective of the study was to assess the serum vascular endothelial growth factor (VEGF) levels in peripheral blood of patients with pregnancy-induced hypertension (PIH) and find association between serum VEGF levels and PIH. Methods. Thirty-five PIH subjects, 35 normal pregnant females, and 20 normal healthy females were included in the study. Detailed history, clinical examination, and relevant biochemical parameters were assessed; serum VEGF levels were estimated using Double-antibody enzyme-linked immunosorbent assay. Results. The study groups were found to be age matched (p = 0.38). VEGF level in the pregnancy-induced hypertensive group (median = 109.19 (3.38 ± 619)) was significantly higher than the normal pregnant (median = 20.82 (1.7–619)) and control (median = 4.92 (1.13–13.07)) group and the difference between these three groups was significant (p < 0.0001). The 3 groups are found to be significantly different in terms of RBS (p = 0.01), urea (p < 0.0001), creatinine (p = 0.0005), AST (p = 0.0032), ALT (p = 0.0007), total protein (p = 0.0004), albumin (p < 0.0001), calcium (p = 0.001), and sodium (p = 0.02), while no statistically significant difference was found between total bilirubin (p = 0.167), direct bilirubin (p = 0.07), uric acid (p = 0.16), and potassium (p = 0.14). Conclusion. Significantly higher levels of serum VEGF were noted in PIH subjects compared to normal pregnant and control subjects. PMID:28133548

  19. Nafamostat Mesilate Inhibits TNF-α-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production.

    Science.gov (United States)

    Kang, Min-Woong; Song, Hee-Jung; Kang, Shin Kwang; Kim, Yonghwan; Jung, Saet-Byel; Jee, Sungju; Moon, Jae Young; Suh, Kwang-Sun; Lee, Sang Do; Jeon, Byeong Hwa; Kim, Cuk-Seong

    2015-05-01

    Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-α (TNF-α). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 µg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-α (3 ng/mL), and it dose dependently prevented the TNF-α-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-α-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-α-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

  20. Aldose reductase inhibitor prevents hyperproliferation and hypertrophy of cultured rat vascular smooth muscle cells induced by high glucose.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Horio, T; Yoshikawa, J

    1995-12-01

    Vascular remodeling is a key process in the pathophysiology of atherosclerosis. Recent evidence suggests that high glucose levels may function as a vascular smooth muscle growth and proliferation-promoting substance. To explore the role of the polyol pathway in this process, we examined the effect of an aldose reductase inhibitor (ARI), epalrestat, on the growth characteristics of cultured rat vascular smooth muscle cells (VSMCs). Epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced proliferative effect as measured by [3H]thymidine incorporation by 67% and 82% in cell number, suggesting ARI as an antimitogenic factor. In VSMCs, epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced incorporation of [3H]leucine by 45% and 58% with the concomitant reduction of the cell size estimated by flowcytometry. Epalrestat (1 mumol/L) also suppressed high glucose-induced intracellular NADH/NAD+ increase and membrane-bound protein kinase C activation. These results indicate that this ARI possesses an antiproliferative and antihypertrophic action on VSMCs induced by high glucose possibly through protein kinase C suppression.

  1. Nicorandil attenuates monocrotaline-induced vascular endothelial damage and pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Makoto Sahara

    pathways in HUVECs, accompanied with the upregulation of both eNOS and Bcl-2 expression. CONCLUSIONS: Nicorandil attenuated MCT-induced vascular endothelial damage and PAH through production of eNOS and anti-apoptotic factors, suggesting that nicorandil might have a promising therapeutic potential for PAH.

  2. Verapamil stereoisomers induce antiproliferative effects in vascular smooth muscle cells via autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Salabei, Joshua K. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202 (United States); Balakumaran, Arun [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Frey, Justin C. [Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Boor, Paul J. [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Treinen-Moslen, Mary [Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555‐0609 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Division of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202 (United States); Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States)

    2012-08-01

    Calcium channel blockers (CCBs) are important in the management of hypertension and limit restenosis. Although CCB efficacy could derive from decreased blood pressure, other mechanisms independent of CCB activity also can contribute to antiproliferative action. To understand mechanisms of CCB-mediated antiproliferation, we studied two structurally dissimilar CCBs, diltiazem and verapamil, in cultured rat vascular smooth muscle cells (VSMC). To elucidate CCB-independent effects, pure stereoisomers of verapamil (R-verapamil, inactive VR; S-verapamil, active, VS) were used. The effects of CCB exposure on cell viability (MTT reduction), cell proliferation ({sup 3}H-thymidine incorporation), VSMC morphology by light and transmission electron microscopy (TEM) and autophagy (LC3I/II, ATG5) were measured. In general, verapamil, VR or VS treatment alone (80 μM) appreciably enhanced MTT absorbance although higher concentrations (VR or VS) slightly decreased MTT absorbance. Diltiazem (140 μM) markedly decreased MTT absorbance (40%) at 120 h. VR or VS treatment inhibited {sup 3}H-thymidine incorporation (24 h) and induced cytological alterations (i.e., karyokinesis, enhanced perinuclear MTT deposition, accumulated perinuclear “vacuoles”). TEM revealed perinuclear “vacuoles” to be aggregates of highly laminated and electron-dense vesicles resembling autophagosomes and lysosomes, respectively. Increased autophagosome activity was confirmed by a concentration-dependent increase in LC3-II formation by Western blotting and by increased perinuclear LC3-GFP{sup +} puncta in verapamil-treated VSMC. Verapamil stereoisomers appeared to decrease perinuclear mitochondrial density. These observations indicate that antiproliferative effects of verapamil stereoisomers are produced by enhanced mitochondrial damage and upregulated autophagy in VSMC. These effects are independent of CCB activity indicating a distinct mechanism of action that could be targeted for more efficacious anti

  3. Measurement of gas flow velocities by laser-induced gratings

    Energy Technology Data Exchange (ETDEWEB)

    Hemmerling, B.; Stampanoni-Panariello, A. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Kozlov, A.D.N. [General Physics Institute, Moscow (Russian Federation)

    1999-08-01

    Time resolved light scattering from laser-induced electrostrictive gratings was used for the determination of flow velocities in air at room temperature. By measuring the velocity profile across the width of a slit nozzle we demonstrated the high spatial resolution (about 200 mm) of this novel technique. (author) 3 figs., 1 ref.

  4. Onset of Flow Induced Tonal Noise in Corrugated Pipe Segments

    NARCIS (Netherlands)

    Rudenko, O.; Nakiboglu, G.; Hirschberg, Abraham

    2014-01-01

    Corrugated pipes combine small-scale rigidity and large-scale flexibility, which make them very useful in industrial applications. The flow through such a pipe can induce strong undesirable tonal noise (whistling) and even drive integrity threatening structural vibrations. Placing a corrugated

  5. Flow-induced phase separation in polymer solutions

    NARCIS (Netherlands)

    Moel, K. de; Flikkema, E.; Szleifer, I.; Brinke, G. ten

    1998-01-01

    A correct description of phase behaviour in polymer solutions requires a coupling between configurational statistics and thermodynamics. The effect of flow-induced chain deformation on the polymer-solvent interaction energy depends on the concentration and on the polymer architecture. It will be dem

  6. Disparity in regional cerebral blood flow during electrically induced seizure

    DEFF Research Database (Denmark)

    Sestoft, D; Meden, P; Hemmingsen, R

    1993-01-01

    This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized on electroencepha...

  7. Flow induced noise modelling for industrial piping systems

    NARCIS (Netherlands)

    Gijrath, H.; Ǎbom, M.

    2003-01-01

    Noise from e.g. gas-transport piping systems becomes more and more a problem for plants located close to urban areas. Too high noise levels are unacceptable and will put limitations on the plant capacity. Flow-induced noise of valves, orifices and headers installed in the installation plays a domina

  8. SHORT COMMINICATION——Involvement of gene expressions in apoptosis of vascular endothelial cells induced by rattlesnake venom

    Institute of Scientific and Technical Information of China (English)

    MIAOJUNYING; SATOHIKOARAKI; 等

    1999-01-01

    Formation of apoptotic bodies is a typical character of apoptotic cell death,but how the processes are controlled is not known.In this study,we compared two apoptosis inducing systems in vascular endothelial cells (VEC).We found that the formation of apoptotic bodies during apoptosis induced by rattlesnake venom,which is an unique and specific apoptosis inducer to vascular endothelial cells,was much faster than that induced by deprivation of survival factors(aFGF and serum).When we blocked the synthesis of mRNAs in cells treated with rattlesnake venom by DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidazole),an inhibitor of transcription,the formation of apoptotic bodies was dramatically inhibited.We examined the expression of P53 gene and found that its expression was much higher inapoptosis induced by rattlesnake venom that that in apoptosis induced by deprivation of aFGF and serum.Our results suggest that gene expression is important and P53 gene may play a major role in inducing the formation of apoptotic bodies in VEC.

  9. Skeletal nutrient vascular adaptation induced by external oscillatory intramedullary fluid pressure intervention

    Directory of Open Access Journals (Sweden)

    Qin Yi-Xian

    2010-03-01

    Full Text Available Abstract Background Interstitial fluid flow induced by loading has demonstrated to be an important mediator for regulating bone mass and morphology. It is shown that the fluid movement generated by the intramedullary pressure (ImP provides a source for pressure gradient in bone. Such dynamic ImP may alter the blood flow within nutrient vessel adjacent to bone and directly connected to the marrow cavity, further initiating nutrient vessel adaptation. It is hypothesized that oscillatory ImP can mediate the blood flow in the skeletal nutrient vessels and trigger vasculature remodeling. The objective of this study was then to evaluate the vasculature remodeling induced by dynamic ImP stimulation as a function of ImP frequency. Methods Using an avian model, dynamics physiological fluid ImP (70 mmHg, peak-peak was applied in the marrow cavity of the left ulna at either 3 Hz or 30 Hz, 10 minutes/day, 5 days/week for 3 or 4 weeks. The histomorphometric measurements of the principal nutrient arteries were done to quantify the arterial wall area, lumen area, wall thickness, and smooth muscle cell layer numbers for comparison. Results The preliminary results indicated that the acute cyclic ImP stimuli can significantly enlarge the nutrient arterial wall area up to 50%, wall thickness up to 20%, and smooth muscle cell layer numbers up to 37%. In addition, 3-week of acute stimulation was sufficient to alter the arterial structural properties, i.e., increase of arterial wall area, whereas 4-week of loading showed only minimal changes regardless of the loading frequency. Conclusions These data indicate a potential mechanism in the interrelationship between vasculature adaptation and applied ImP alteration. Acute ImP could possibly initiate the remodeling in the bone nutrient vasculature, which may ultimately alter blood supply to bone.

  10. Amniotic fluid stem cells morph into a cardiovascular lineage: analysis of a chemically induced cardiac and vascular commitment.

    Science.gov (United States)

    Maioli, Margherita; Contini, Giovanni; Santaniello, Sara; Bandiera, Pasquale; Pigliaru, Gianfranco; Sanna, Raimonda; Rinaldi, Salvatore; Delitala, Alessandro P; Montella, Andrea; Bagella, Luigi; Ventura, Carlo

    2013-01-01

    Mouse embryonic stem cells were previously observed along with mesenchymal stem cells from different sources, after being treated with a mixed ester of hyaluronan with butyric and retinoic acids, to show a significant increase in the yield of cardiogenic and vascular differentiated elements. The aim of the present study was to determine if stem cells derived from primitive fetal cells present in human amniotic fluid (hAFSCs) and cultured in the presence of a mixture of hyaluronic (HA), butyric (BU), and retinoic (RA) acids show a higher yield of differentiation toward the cardiovascular phenotype as compared with untreated cells. During the differentiation process elicited by exposure to HA + BU + RA, genes controlling pluripotency and plasticity of stem cells, such as Sox2, Nanog, and Oct4, were significantly downregulated at the transcriptional level. At this point, a significant increase in expression of genes controlling the appearance of cardiogenic and vascular lineages in HA + BU + RA-treated cells was observed. The protein expression levels typical of cardiac and vascular phenotypes, evaluated by Western blotting, immunofluorescence, and flow cytometry, were higher in hAFSCs cultured in the presence of HA + BU + RA, as compared with untreated control cells. Appearance of the cardiac phenotype was further inferred by ultrastructural analysis using transmission and scanning electron microscopy. These results demonstrate that a mixture of HA + BU + RA significantly increased the yield of elements committed toward cardiac and vascular phenotypes, confirming what we have previously observed in other cellular types.

  11. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

    OpenAIRE

    Marjo M P C Donners; Bai, Lili; Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat; Cleutjens, Kitty B.J.M.; Shi, Guo-Ping; BIESSEN, Erik; Heeneman, Sylvia

    2016-01-01

    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with w...

  12. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  13. In vivo vascular wall tissue characterization using a strain tensor measuring (STM) technique for flow-mediated vasodilation analyses

    Science.gov (United States)

    Mahmoud, Ahmed M.; Frisbee, Jefferson C.; D'Audiffret, Alexandre; Mukdadi, Osama M.

    2009-10-01

    Endothelial dysfunction is considered to be a key factor in the development of atherosclerosis, and the measurement of flow-mediated vasodilation (FMD) in brachial and other conduit arteries has become a common method to assess the status of endothelial function in vivo. Based on the direct relationship between the FMD response and local shear stress on the conduit brachial artery endothelium, we hypothesize that measuring relevant changes in the brachial wall strain tensor would provide a non-invasive tool for assessing vascular mechanics during post-occlusion reactive hyperemia. Direct measurement of the wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during post-occlusion reactive hyperemia and/or FMD, including local velocities and displacements, diameter change, local strain tensor and strain rates. The STM technique utilizes sequences of B-mode ultrasound images as its input with no extra hardware requirement, and its algorithm starts with segmenting a region of interest within the artery and providing the acquisition parameters. Then a block matching technique based on speckle tracking is employed to measure the frame-to-frame local velocities. Displacements, diameter change, local strain tensor and strain rates are then calculated by integrating or differentiating velocity components. The accuracy of the STM algorithm was assessed in vitro using phantom studies, where an average error of 7% was reported using different displacement ranging from 100 µm to 1000 µm. Furthermore, in vivo studies using human subjects were performed to test the STM algorithm during pre- and post-occlusion. Good correlations (|r| >0.5, P < 0.05) were found between the post-occlusion responses of diameter change and local wall strains. Results indicate the validity and versatility of

  14. In vivo vascular wall tissue characterization using a strain tensor measuring (STM) technique for flow-mediated vasodilation analyses

    Energy Technology Data Exchange (ETDEWEB)

    Mahmoud, Ahmed M; Mukdadi, Osama M [Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, WV 26506 (United States); Frisbee, Jefferson C [Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, WV 26506 (United States); D' Audiffret, Alexandre [Division of Vascular and Endovascular Surgery, West Virginia University, Morgantown, WV 26506 (United States)], E-mail: sam.mukdadi@mail.wvu.edu

    2009-10-21

    Endothelial dysfunction is considered to be a key factor in the development of atherosclerosis, and the measurement of flow-mediated vasodilation (FMD) in brachial and other conduit arteries has become a common method to assess the status of endothelial function in vivo. Based on the direct relationship between the FMD response and local shear stress on the conduit brachial artery endothelium, we hypothesize that measuring relevant changes in the brachial wall strain tensor would provide a non-invasive tool for assessing vascular mechanics during post-occlusion reactive hyperemia. Direct measurement of the wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during post-occlusion reactive hyperemia and/or FMD, including local velocities and displacements, diameter change, local strain tensor and strain rates. The STM technique utilizes sequences of B-mode ultrasound images as its input with no extra hardware requirement, and its algorithm starts with segmenting a region of interest within the artery and providing the acquisition parameters. Then a block matching technique based on speckle tracking is employed to measure the frame-to-frame local velocities. Displacements, diameter change, local strain tensor and strain rates are then calculated by integrating or differentiating velocity components. The accuracy of the STM algorithm was assessed in vitro using phantom studies, where an average error of 7% was reported using different displacement ranging from 100 {mu}m to 1000 {mu}m. Furthermore, in vivo studies using human subjects were performed to test the STM algorithm during pre- and post-occlusion. Good correlations (|r| >0.5, P < 0.05) were found between the post-occlusion responses of diameter change and local wall strains. Results indicate the validity and

  15. Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways

    Energy Technology Data Exchange (ETDEWEB)

    Aguado, Andrea; Galán, María; Zhenyukh, Olha; Wiggers, Giulia A.; Roque, Fernanda R. [Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid (Spain); Redondo, Santiago [Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, 28040, Madrid (Spain); Peçanha, Franck [Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid (Spain); Martín, Angela [Departamento de Bioquímica, Fisiología y Genética Molecular, Universidad Rey Juan Carlos, 28922, Alcorcón (Spain); Fortuño, Ana [Área de Ciencias Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, 31008, Pamplona (Spain); Cachofeiro, Victoria [Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, 28040, Madrid (Spain); Tejerina, Teresa [Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, 28040, Madrid (Spain); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid (Spain); and others

    2013-04-15

    Mercury exposure is known to increase cardiovascular risk but the underlying cellular mechanisms remain undetermined. We analyzed whether chronic exposure to HgCl{sub 2} affects vascular structure and the functional properties of vascular smooth muscle cells (VSMC) through oxidative stress/cyclooxygenase-2 dependent pathways. Mesenteric resistance arteries and aortas from Wistar rats treated with HgCl{sub 2} (first dose 4.6 mg kg{sup −1}, subsequent doses 0.07 mg kg{sup −1} day{sup −1}, 30 days) and cultured aortic VSMC stimulated with HgCl{sub 2} (0.05–5 μg/ml) were used. Treatment of rats with HgCl{sub 2} decreased wall thickness of the resistance and conductance vasculature, increased the number of SMC within the media and decreased SMC nucleus size. In VSMCs, exposure to HgCl{sub 2}: 1) induced a proliferative response and a reduction in cell size; 2) increased superoxide anion production, NADPH oxidase activity, gene and/or protein levels of the NADPH oxidase subunit NOX-1, the EC- and Mn-superoxide dismutases and cyclooxygenase-2 (COX-2); 3) induced activation of ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized the proliferative response and the altered cell size induced by HgCl{sub 2}. Blockade of ERK1/2 and p38 signaling pathways abolished the HgCl{sub 2}-induced Nox1 and COX-2 expression and normalized the alterations induced by mercury in cell proliferation and size. In conclusion, long exposure of VSMC to low doses of mercury activates MAPK signaling pathways that result in activation of inflammatory proteins such as NADPH oxidase and COX-2 that in turn induce proliferation of VSMC and changes in cell size. These findings offer further evidence that mercury might be considered an environmental risk factor for cardiovascular disease. - Highlights: ► Chronic HgCl{sub 2} exposure induces vascular remodeling. ► HgCl{sub 2} induces proliferation and decreased cell size in vascular smooth muscle cells. ► HgCl{sub 2} induces

  16. FLAIR vascular hyperintensities and dynamic 4D angiograms for the estimation of collateral blood flow in posterior circulation occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Foerster, Alex; Wenz, Holger; Kerl, Hans Ulrich; Al-Zghloul, Mansour; Habich, Sonia; Groden, Christoph [University of Heidelberg, Department of Neuroradiology, Universitaetsmedizin Mannheim, Mannheim (Germany)

    2014-09-15

    The objectives of this paper are to assess collateral blood flow in posterior circulation occlusion by MRI-based approaches (fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs), collateralization on dynamic 4D angiograms) and investigate its relation to ischemic lesion size and growth. In 28 patients with posterior cerebral artery (PCA) and 10 patients with basilar artery (BA) occlusion, MRI findings were analyzed, with emphasis on distal FVH and collateralization on dynamic 4D angiograms. In PCA occlusion, distal FVH was observed in 18/29 (62.1 %), in BA occlusion, in 8/10 (80 %) cases. Collateralization on dynamic 4D angiograms was graded 1 in 8 (27.6 %) patients, 2 in 1 (3.4 %) patient, 3 in 12 (41.4 %) patients, and 4 in 8 (27.6 %) patients with PCA occlusion and 0 in 1 (10 %) patient, 2 in 3 (30 %) patients, 3 in 1 (10 %) patient, and 4 in 5 (50 %) patients with BA occlusion. FVH grade showed neither correlation with initial or follow-up diffusion-weighted image (DWI) lesion size nor DWI-perfusion-weighted imaging (PWI) mismatch ratio. Collateralization on dynamic 4D angiograms correlated inversely with initial DWI lesion size and moderately with the DWI-(PWI) mismatch ratio. The combination of distal FVH and collateralization grade on dynamic 4D angiograms correlated inversely with initial as well as follow-up DWI lesion size and highly with the DWI-PWI mismatch ratio. In posterior circulation occlusion, FVH is a frequent finding, but its prognostic value is limited. Dynamic 4D angiograms are advantageous to examine and graduate collateral blood flow. The combination of both parameters results in an improved characterization of collateral blood flow and might have prognostic relevance. (orig.)

  17. Advanced 3D mesh manipulation in stereolithographic files and post-print processing for the manufacturing of patient-specific vascular flow phantoms

    Science.gov (United States)

    O'Hara, Ryan P.; Chand, Arpita; Vidiyala, Sowmya; Arechavala, Stacie M.; Mitsouras, Dimitrios; Rudin, Stephen; Ionita, Ciprian N.

    2016-03-01

    Complex vascular anatomies can cause the failure of image-guided endovascular procedures. 3D printed patient-specific vascular phantoms provide clinicians and medical device companies the ability to preemptively plan surgical treatments, test the likelihood of device success, and determine potential operative setbacks. This research aims to present advanced mesh manipulation techniques of stereolithographic (STL) files segmented from medical imaging and post-print surface optimization to match physiological vascular flow resistance. For phantom design, we developed three mesh manipulation techniques. The first method allows outlet 3D mesh manipulations to merge superfluous vessels into a single junction, decreasing the number of flow outlets and making it feasible to include smaller vessels. Next we introduced Boolean operations to eliminate the need to manually merge mesh layers and eliminate errors of mesh self-intersections that previously occurred. Finally we optimize support addition to preserve the patient anatomical geometry. For post-print surface optimization, we investigated various solutions and methods to remove support material and smooth the inner vessel surface. Solutions of chloroform, alcohol and sodium hydroxide were used to process various phantoms and hydraulic resistance was measured and compared with values reported in literature. The newly mesh manipulation methods decrease the phantom design time by 30 - 80% and allow for rapid development of accurate vascular models. We have created 3D printed vascular models with vessel diameters less than 0.5 mm. The methods presented in this work could lead to shorter design time for patient specific phantoms and better physiological simulations.

  18. Gastric vascular and motor responses to anaphylactic hypotension in anesthetized rats, in comparison to those with hemorrhagic or vasodilator-induced hypotension.

    Science.gov (United States)

    Kuda, Yuhichi; Shibamoto, Toshishige; Zhang, Tao; Yang, Wei; Tanida, Mamoru; Kurata, Yasutaka

    2017-01-31

    Anaphylactic shock is life-threatening, but pathophysiology of the stomach lesion remains unclear. We determined gastric hemodynamics and gastric functions during anaphylactic hypotension, as compared to hypotension induced by hemorrhage or sodium nitroprusside (SNP) in anesthetized and ovalbumin-sensitized Sprague-Dawley rats. Systemic arterial pressure, portal venous pressure, and gastric arterial blood flow were measured, and gastric vascular resistance (GVR) was determined. Separately, the intragastric pressure (IGP) and gastric effluent, as a measure of gastric flux, were continuously measured. During anaphylaxis, GVR decreased only transiently at 0.5 min, followed by an increase. IGP increased markedly, while gastric flux decreased. During hemorrhage, GVR and IGP increased, while gastric flux did not change. When SNP was injected, both GVR and IGP decreased and gastric flux increased only just after injection. In conclusion, gastric vasodilatation occurs only transiently after antigen injection, and gastric motility increases, but gastric emptying deceases during anaphylactic hypotension in anesthetized rats.

  19. Shock-induced turbulent flow in baffle systems

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, A.L. [Lawrence Livermore National Lab., CA (United States); Reichenbach, H. [Fraunhofer-Institut fuer Kurzzeitdynamik - Ernst-Mach-Institut (EMI), Freiburg im Breisgau (Germany)

    1993-07-01

    Experiments are described on shock propagation through 2-D aligned and staggered baffle systems. Flow visualization was provided by shadow and schlieren photography, recorded by the Cranz-Schardin camera. Also single-frame, infinite-fringe, color interferograms were used. Intuition suggests that this is a rather simple 2-D shock diffraction problem. However, flow visualization reveals that the flow rapidly evolved into a complex 3-D turbulent mixing problem. Mushroom-shaped mixing regions blocked the flow into the next baffle orifice. Thus energy was transferred from the directed kinetic energy (induced by the shock) to rotational energy of turbulent mixing, and then dissipated by molecular effects. These processes dramatically dissipate the strength of the shock wave. The experiments provide an excellent test case that could be used to assess the accuracy of computer code calculations of such problems.

  20. Simulations of a Liquid Hydrogen Inducer at Low-Flow Off-Design Flow Conditions

    Science.gov (United States)

    Hosangadi, A.; Ahuja, V.; Ungewitter, R. J.

    2005-01-01

    The ability to accurately model details of inlet back flow for inducers operating a t low-flow, off-design conditions is evaluated. A sub-scale version of a three-bladed liquid hydrogen inducer tested in water with detailed velocity and pressure measurements is used as a numerical test bed. Under low-flow, off-design conditions the length of the separation zone as well as the swirl velocity magnitude was under predicted with a standard k-E model. When the turbulent viscosity coefficient was reduced good comparison was obtained a t all the flow conditions examined with both the magnitude and shape of the profile matching well with the experimental data taken half a diameter upstream of the leading edge. The velocity profiles and incidence angles a t the leading edge itself were less sensitive to the back flow length predictions indicating that single-phase performance predictions may be well predicted even if the details of flow separation modeled are incorrect. However, for cavitating flow situations the prediction of the correct swirl in the back flow and the pressure depression in the core becomes critical since it leads to vapor formation. The simulations have been performed using the CRUNCH CFD(Registered Trademark) code that has a generalized multi-element unstructured framework and a n advanced multi-phase formulation for cryogenic fluids. The framework has been validated rigorously for predictions of temperature and pressure depression in cryogenic fluid cavities and has also been shown to predict the cavitation breakdown point for inducers a t design conditions.

  1. Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent

    OpenAIRE

    2010-01-01

    Chronic lead exposure induces hypertension in humans and animals, affecting endothelial function. However, studies concerning acute cardiovascular effects are lacking. We investigated the effects of acute administration of a high concentration of lead acetate (100 µΜ) on the pressor response to phenylephrine (PHE) in the tail vascular bed of male Wistar rats. Animals were anesthetized with sodium pentobarbital and heparinized. The tail artery was dissected and cannulated for drug infusio...

  2. Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

    Directory of Open Access Journals (Sweden)

    Hales Charles A

    2011-02-01

    Full Text Available Abstract Background CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood. Methods In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats. Results We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP, ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats. Conclusions The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.

  3. Iloprost up-regulates vascular endothelial growth factor expression in human dental pulp cells in vitro and enhances pulpal blood flow in vivo.

    Science.gov (United States)

    Limjeerajarus, Chalida Nakalekha; Osathanon, Thanaphum; Manokawinchoke, Jeeranan; Pavasant, Prasit

    2014-07-01

    Prostacyclin (PGI2) is a biomolecule capable of enhancing angiogenesis and cellular proliferation. We investigated the influence of a PGI2 analogue (iloprost) on dental pulp revascularization in vitro and in vivo by using human dental pulp cells (HDPCs) and a rat tooth injury model, respectively. Iloprost stimulated the human dental pulp cell mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and platelet-derived growth factor (PDGF) in a significant dose-dependent manner. This mRNA up-regulation was significantly inhibited by pretreatment with a PGI2 receptor antagonist and forskolin (a protein kinase A activator). In contrast, a protein kinase A inhibitor significantly enhanced the iloprost-induced mRNA expression of VEGF, FGF-2, and PDGF. Pretreatment with a fibroblast growth factor receptor inhibitor attenuated the VEGF, FGF-2, and PDGF mRNA expression, indicating opposing regulatory mechanisms. The effect of iloprost on the dental pulp was investigated in vivo by using a rat molar pulp injury model. The iloprost-treated group exhibited a significant increase in pulpal blood flow at 72 hours compared with control. The present study indicates that iloprost may be a candidate agent to promote neovascularization in dental pulp tissue, suggesting the potential clinical use of iloprost in vital pulp therapy. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Evidence that the contraction-induced rapid hyperemia in rabbit masseter muscle is based on a mechanosensitive mechanism, not shared by cutaneous vascular beds.

    Science.gov (United States)

    Turturici, Marco; Mohammed, Mazher; Roatta, Silvestro

    2012-08-15

    Several mechanisms have been hypothesized to contribute to the rapid hyperemia at the onset of exercise. The aim of the present study was to investigate the role played by the mechanosensitivity of the vascular network. In 12 anesthetized rabbits blood flow was recorded from the exclusively muscular masseteric artery in response to brief spontaneous contractions (BSC) of the masseter muscle, artery occlusion (AO), muscle compression (MC), and muscle stretch (MS). Activation of masseter muscle was monitored by electromyography (EMG). Responses to AO were also recorded from the mostly cutaneous facial and the central ear arteries. Five animals were also tested in the awake condition. The hyperemic response to BSC (peak amplitude of 394 ± 82%; time to peak of 1.8 ± 0.8 s) developed with a latency of 300-400 ms from the beginning of the EMG burst and 200-300 ms from the contraction-induced transient flow reduction. This response was neither different from the response to AO (peak amplitude = 426 ± 158%), MC, and MS (P = 0.23), nor from the BSC response in the awake condition. Compared with the masseteric artery, the response to AO was markedly smaller both in the facial (83 ± 18%,) and in the central ear artery (68 ± 20%) (P < 0.01). In conclusion, the rapid contraction-induced hyperemia can be replicated by a variety of stimuli affecting transmural pressure in muscle blood vessels and is thus compatible with the Bayliss effect. This prominent mechanosensitivity appears to be a characteristic of muscle and not cutaneous vascular beds.

  5. Effects of prolonged ingestion of epigallocatechin gallate on diabetes type 1-induced vascular modifications in the erectile tissue of rats.

    Science.gov (United States)

    Lombo, C; Morgado, C; Tavares, I; Neves, D

    2016-07-01

    Diabetes Mellitus type 1 is a metabolic disease that predisposes to erectile dysfunction, partly owing to structural and molecular changes in the corpus cavernosum (CC) vessels. The aim of this study was to determine the effects of early treatment with the antioxidant epigallocatechin gallate (EGCG) in cavernous diabetes-induced vascular modifications. Diabetes was induced in two groups of young Wistar rats; one group was treated with EGCG for 10 weeks. A reduction in smooth muscle content was observed in the CC of diabetic rats, which was significantly attenuated with EGCG consumption. No differences were observed among groups, neither in the expression of VEGF assayed by western blotting nor in the immunofluorescent labeling of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2). VEGFR2 was restricted to the endothelium, whereas VEGF and VEGFR1 co-localized in the smooth muscle layer. With regard to the Angiopoietin/Tie-2 system, no quantitative differences in Angiopoietin 1 were observed among the experimental groups. Ang1 localization was restricted to the smooth muscle layer, and receptor Tie2 and Angiopoietin 2 were both expressed in the endothelium. In brief, our results suggest that EGCG consumption prevented diabetes-induced loss of cavernous smooth muscle but does not affect vascular growth factor expression in young rats.

  6. Apoptosis of vascular smooth muscle cells induced by cholesterol and its oxides in vitro and in vivo.

    Science.gov (United States)

    Yin, J; Chaufour, X; McLachlan, C; McGuire, M; White, G; King, N; Hambly, B

    2000-02-01

    The ability of cholesterol and its oxides to induce apoptosis in vascular smooth muscle cells in tissue culture and in a rabbit model of atherosclerosis was evaluated. Apoptosis was detected using DNA laddering and in situ end-labelling of fragmented DNA. Cholesterol oxides, but not cholesterol, were found to inhibit proliferation and induce apoptosis of vascular smooth muscle cells in tissue culture. 7-ketocholesterol was found to be the most potent inhibitor of proliferation, while 25-hydroxycholesterol was found to be the most potent inducer of apoptosis. These data suggest that the inhibition of proliferation and the induction of apoptosis by cholesterol oxides within vascular smooth muscle cells use different pathways, suggesting a differential role for these cholesterol oxides within the arterial wall. Cholesterol feeding after balloon injury in a rabbit model of atherosclerosis is known to result in the accumulation of cholesterol oxides. However, we found that cholesterol feeding had no effect on the level of apoptosis in the rabbit aortic wall after balloon injury, suggesting that the major factor determining apoptosis in our model was the balloon injury.

  7. Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers

    Directory of Open Access Journals (Sweden)

    Antonio Garcia Soares

    2017-01-01

    Full Text Available Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA and thoracic aorta (TA. Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.

  8. Protective effect of crocin against apoptosis induced by subchronic exposure of the rat vascular system to diazinon.

    Science.gov (United States)

    Razavi, Bibi Marjan; Hosseinzadeh, Hossein; Abnous, Khalil; Khoei, Alireza; Imenshahidi, Mohsen

    2016-07-01

    Research has suggested that natural antioxidant, crocin, an active ingredient of saffron, may protect against diazinon (DZN)-induced toxicity. Although increased production of lipid peroxidation by DZN in rat aorta has been shown previously, the effects of DZN on oxidative stress-induced apoptosis in vascular system have not been evaluated. In this study, the effect of crocin on DZN-induced apoptosis in rat vascular system was investigated. The rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, and 50 mg/kg/day, intraperitoneally (i.p.)) + DZN, vitamin E (200 IU/kg, i.p., 3 days a week) + DZN, and crocin (50 mg/kg/day, i.p.). The treatments were continued for 4 weeks. Levels of apoptotic (Bax, caspase 3, and caspase 9) and antiapoptotic proteins (Bcl2) were analyzed by Western blotting. Transcript levels of Bax and Bcl2 genes were determined using quantitative real-time polymerase chain reaction. Results showed DZN-induced apoptosis by activation of caspase 9 and caspase 3 and by increasing the Bax/Bcl2 ratio (both protein and messenger RNA levels). Crocin and vitamin E inhibited apoptosis induced by DZN. In summary, subchronic exposure to DZN induced caspase-mediated apoptosis, and crocin reduced the toxic effects of DZN by inhibiting apoptosis in aortic tissue.

  9. Crucial role of Toll-like receptors in the zinc/nickel-induced inflammatory response in vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsou, Tsui-Chun, E-mail: tctsou@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Liou, Saou-Hsing; Yeh, Szu-Ching; Tsai, Feng-Yuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Chao, How-Ran [Emerging Compounds Research Center, Department of Environmental Science and Engineering, National Pingtung University and Science and Technology, Neipu, Pingtung 912, Taiwan (China)

    2013-12-15

    Our previous studies indicated that zinc induced inflammatory response in both vascular endothelial cells and promonocytes. Here, we asked if other metals could cause the similar effect on vascular endothelial cells and tried to determine its underlying mechanism. Following screening of fifteen metals, zinc and nickel were identified with a marked proinflammatory effect, as determined by ICAM-1 and IL-8 induction, on human umbilical vein endothelial cells (HUVECs). Inhibiting protein expression of myeloid differentiation primary response protein-88 (MyD88), a Toll-like receptor (TLR) adaptor acting as a TLR-signaling transducer, significantly attenuated the zinc/nickel-induced inflammatory response, suggesting the critical roles of TLRs in the inflammatory response. Blockage of TLR-4 signaling by CLI-095, a TLR-4 inhibitor, completely inhibited the nickel-induced ICAM-1 and IL-8 expression and NFκB activation. The same CLI-095 treatment significantly blocked the zinc-induced IL-8 expression, however with no significant effect on the ICAM-1 expression and a minor inhibitory effect on the NFκB activation. The finding demonstrated the differential role of TLR-4 in regulation of the zinc/nickel-induced inflammatory response, where TLR-4 played a dominant role in NFκB activation by nickel, but not by zinc. Moreover, inhibition of NFκB by adenovirus-mediated IκBα expression and Bay 11-7025, an inhibitor of cytokine-induced IκB-α phosphorylation, significantly attenuated the zinc/nickel-induced inflammatory responses, indicating the critical of NFκB in the process. The study demonstrates the crucial role of TLRs in the zinc/nickel-induced inflammatory response in vascular endothelial cells and herein deciphers a potential important difference in NFκB activation via TLRs. The study provides a molecular basis for linkage between zinc/nickel exposure and pathogenesis of the metal-related inflammatory vascular disease. - Highlights: • Both zinc and nickel cause

  10. Age does not affect uterine resistance to vascular flow in patients undergoing oocyte donation.

    Science.gov (United States)

    Guanes, P P; Remohí, J; Gallardo, E; Valbuena, D; Simón, C; Pellicer, A

    1996-08-01

    To determine whether uterine vasculature is affected by age using oocyte donation as an in vivo model. Prospective longitudinal study in which recipients were grouped according to age. They underwent a successful oocyte donation cycle, and single pregnancies were followed during the first trimester by color Doppler ultrasound in uterine arteries. Oocyte donation and IVF program at the Instituto Valenciano de Infertilidad. Serum E2, P, and hCG levels in single ovum donation pregnancies; pulsatility and resistance indexes in uterine arteries during initial pregnancy. Similar serum levels of E2, P, and hCG in both groups of patients were observed. There was no difference between groups regarding the flow indexes analyzed. The increased incidence of early pregnancy losses observed in patients > 40 years cannot be attributed to defective response of uterine vasculature to exogenous hormone replacement. Thus, uterine aging does not appear to be a factor influencing the poor reproductive performance of women with advancing age.

  11. The effect of hepatic vascular exclusion on hepatic blood flow and oxygen supply--uptake ratio in the pig.

    Science.gov (United States)

    López Santamaria, M; Gamez, M; Murcia, J; Paz Cruz, J A; Bueno, J; Canser, E; Qi, B; Lobato, R; Martinez, L; Jara, P; Tovar, J A

    1997-10-01

    The hemodynamic disturbances produced by total hepatic vascular exclusion (THVE) for 40 minutes were studied in 7 pigs (19-22 kg). THVE was produced by clamping the hepatic pedicle and inferior vena cava, above and below the liver, for a 40-minutes period, followed by unclamping. Compared to baseline values, 30 minutes after onset of THVE, there was a decrease in cardiac output (3.86 +/- 0.55 vs 1.23 +/- 0.23 L x min-1), systemic arterial pressure (97.54 +/- 13.58 vs 43.43 +/- 11.38 mm Hg), and pulmonary artery pressure (16.57 +/- 6.38 vs 12.57 +/- 3.58) and an increase in systemic and pulmonary vascular resistance (1772 +/- 198 vs 2351 +/- 462, and 182 +/- 66 vs 361 +/- 124 dyn x s x cm-5 respectively). As a result of diminished cardiac output, the systemic oxygen supply decreased (461 +/- 131 vs 101 +/- 46 ml x min-1), but the systemic oxygen extraction rate rose from 17.3% t0 31.2%. Thirty minutes after unclamping, the changes had reversed and all the parameters tended to normalize. Total hepatic blood flow 30 minutes after unclamping was higher than at baseline (5.08 +/- 1.2 vs 6.66 +/- 0.67 ml x min-1 x 100 g-1), because of the increase in portal blood flow (4.52 +/- 1.21 vs 6.07 +/- 0.70 ml x min-1 x 100 g-1). There were no significant differences in hepatic oxygen supply and uptake at baseline and after unclamping (152.6 +/- 23.0 vs 187.0 +/- 34.7 and 22.7 +/- 4.9 vs 28.7 +/- 8.4 ml O2 respectively). AST rose (29 +/- 7 vs 136 +/- 91 U/l), but there was no change in the remaining liver enzymes, glucose, creatinine and serum electrolytes, so we conclude that the hemodynamic disturbances produced by 40 minutes of THVE are manageable and spontaneously reversible. Liver metabolism was not greatly disturbed, so THVE was judged to be a viable technique to be added to the surgeon's range of options.

  12. Numerical investigation on vibration and noise induced by unsteady flow in an axial-flow pump

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Eryun; Ma, Zui Ling; Yang, Ai Ling; Nan, Guo Fang [School of Energy and Power Engineering, University of Shanghai for Science and Technology, Shanghai (China); Zhao, Gai Ping [School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai (China); Li, Guo Ping [Shanghai Marine Equipment Research Institute, Shanghai (China)

    2016-12-15

    Full-scale structural vibration and noise induced by flow in an axial-flow pump was simulated by a hybrid numerical method. An unsteady flow field was solved by a large eddy simulation-based computational fluid dynamics commercial code, Fluent. An experimental validation on pressure fluctuations was performed to impose an appropriate vibration exciting source. The consistency between the computed results and experimental tests were interesting. The modes of the axial-flow pump were computed by the finite element method. After that, the pump vibration and sound field were solved using a coupled vibro-acoustic model. The numerical results indicated that the the blade-passing frequency was the dominant frequency of the vibration acceleration of the pump. This result was consistent with frequency spectral characteristics of unsteady pressure fluctuation. Finally, comparisons of the vibration acceleration between the computed results and the experimental test were conducted. These comparisons validated the computed results. This study shows that using the hybrid numerical method to evaluate the flow-induced vibration and noise generated in an axial-flow pump is feasible.

  13. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  14. Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase.

    Science.gov (United States)

    Park, Ji Young; Choi, Young Whan; Yun, Jung Wook; Bae, Jin Ung; Seo, Kyo Won; Lee, Seung Jin; Park, So Youn; Kim, Chi Dae

    2012-01-01

    Gomisin J (GJ) is a lignan contained in Schisandra chinensis (SC) which is a well-known medicinal herb for improvement of cardiovascular symptoms in Korean. Thus, the present study examined the vascular effects of GJ, and also determined the mechanisms involved. Exposure of rat thoracic aorta to GJ (1-30μg/ml) resulted in a concentration-dependent vasorelaxation, which was more prominent in the endothelium (ED)-intact aorta. ED-dependent relaxation induced by GJ was markedly attenuated by pretreatment with L-NAME, a nitric oxide synthase (NOS) inhibitor. In the intact endothelial cells of rat thoracic aorta, GJ also enhanced nitric oxide (NO) production. In studies using human coronary artery endothelial cells, GJ enhanced phosphorylation of endothelial NOS (eNOS) at Ser(1177) with increased cytosolic translocation of eNOS, and subsequently increased NO production. These effects of GJ were attenuated not only by calcium chelators including EGTA and BAPTA-AM, but also by LY294002, a PI3K/Akt inhibitor, indicating calcium- and PI3K/Akt-dependent activation of eNOS by GJ. Moreover, the levels of intracellular calcium were increased immediately after GJ administration, but Akt phosphorylation was started to increase at 20min of GJ treatment. Based on these results with the facts that ED-dependent relaxation occurred rapidly after GJ treatment, it was suggested that the ED-dependent vasorelaxant effects of GJ were mediated mainly by calcium-dependent activation of eNOS with subsequent production of endothelial NO.

  15. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis.

    Science.gov (United States)

    Enns, Winnie; von Rossum, Anna; Choy, Jonathan

    2015-05-17

    Vascular rejection that leads to transplant arteriosclerosis (TA) is the leading representation of chronic heart transplant failure. In TA, the immune system of the recipient causes damage of the arterial wall and dysfunction of endothelial cells and smooth muscle cells. This triggers a pathological repair response that is characterized by intimal thickening and luminal occlusion. Understanding the mechanisms by which the immune system causes vasculature rejection and TA may inform the development of novel ways to manage graft failure. Here, we describe a mouse aortic interposition model that can be used to study the pathogenic mechanisms of vascular rejection and TA. The model involves grafting of an aortic segment from a donor animal into an allogeneic recipient. Rejection of the artery segment involves alloimmune reactions and results in arterial changes that resemble vascular rejection. The basic technical approach we describe can be used with different mouse strains and targeted interventions to answer specific questions related to vascular rejection and TA.

  16. Ameliorative role of Atorvastatin and Pitavastatin in L-Methionine induced vascular dementia in rats

    OpenAIRE

    Koladiya, Rajeshkumar U; JAGGI,AMTESHWAR S.; Singh, Nirmal; Sharma, Bhupesh K

    2008-01-01

    Background Statins, HMG-CoA reductase inhibitors, are widely prescribed drugs for dyslipidemias. Recent studies have indicated number of cholesterol independent actions of statins including their beneficial effects on vascular endothelial dysfunction and memory deficits associated with dementia of Alzheimer's type. However the potential of statins in dementia of vascular origin still remains to be explored. Therefore, the present study has been designed to investigate the effect of Atorvastat...

  17. Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-hua; WEI Wei; XU Hao; WANG Yan-yan; WU Wen-xi

    2007-01-01

    Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

  18. Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension.

    Science.gov (United States)

    Harris, David M; Cohn, Heather I; Pesant, Stéphanie; Zhou, Rui-Hai; Eckhart, Andrea D

    2007-11-01

    More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.

  19. Effects of angiotensin Ⅱ receptor antagonist olmesartan on renal hemodynamic variables and vascular structural properties in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    SONG Hui-fen; CHEN Jian-fei; SUN Ning-ling; LI Hong-wei

    2011-01-01

    Background Diabetic nephropathy is a major cause of renal failure in diabetes mellitus (DM). It has been known that renin-angiotensin system (RAS) blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin Ⅱ receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin (STZ)-induced DM rats.Methods DM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment (OLM+DM) group. The normal group (non-DM) were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated: slope of flow-pressure (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature), slope of pressure-GFR (glomerular filtration capacity against pressure)and threshold pressure for beginning filtration at pressure-GFR (preglomerular to postglomerular vascular resistance ratio). Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.Results The body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight,urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM+DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats

  20. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Saygili, Erol, E-mail: erol.saygili@med.uni-duesseldorf.de [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Noor-Ebad, Fawad; Schröder, Jörg W.; Mischke, Karl [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Saygili, Esra [Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Rackauskas, Gediminas [Department of Cardiovascular Medicine, Vilnius University Hospital Santariskiu Klinikos, Vilnius University (Lithuania); Marx, Nikolaus [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Kelm, Malte; Rana, Obaida R. [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany)

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing factors

  1. Wind-Induced Ventilation Based on the Separated Flow Region

    Directory of Open Access Journals (Sweden)

    Mostafa Rahimi

    2016-01-01

    Full Text Available An experimental investigation was conducted to study the potential use of the pressure reduction within the separated flow region followed by the wake at the leeward direction of a solid surface in natural ventilation of buildings. Air flow with mean velocity up to 7 m/s was directed onto a solid surface (circular plate and a semi-spherical surface behind which the top end of a vertical vent pipe had been placed. Pressure reduction at the exit section of the pipe, which was well inside the separated flow region, induced an air flow within the pipe. This air flow rate from the stagnant surroundings into the wake region was measured under different geometrical configurations and for various wind velocities. The study revealed that the pressure reduction within the separated flow region would be applicable for natural ventilation of different spaces at least as an auxiliary system. The spaces include; sanitary places, crop protection stocks, industrial workshops and other spaces where no regular ventilation is required.

  2. Vascular relaxation induced by C-type natriuretic peptide involves the ca2+/NO-synthase/NO pathway.

    Directory of Open Access Journals (Sweden)

    Fernanda A Andrade

    Full Text Available AIMS: C-type natriuretic peptide (CNP and nitric oxide (NO are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3 contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery. MAIN METHODS: Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry. KEY FINDINGS: CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas. SIGNIFICANCE: These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.

  3. Activation of integrin α5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells.

    Science.gov (United States)

    Sun, Xiaoli; Fu, Yi; Gu, Mingxia; Zhang, Lu; Li, Dan; Li, Hongliang; Chien, Shu; Shyy, John Y-J; Zhu, Yi

    2016-01-19

    Local flow patterns determine the uneven distribution of atherosclerotic lesions. Membrane lipid rafts and integrins are crucial for shear stress-regulated endothelial function. In this study, we investigate the role of lipid rafts and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under atheroprone versus atheroprotective flow. Lipid raft proteins were isolated from ECs exposed to oscillatory shear stress (OS) or pulsatile shear stress, and then analyzed by quantitative proteomics. Among 396 proteins redistributed in lipid rafts, integrin α5 was the most significantly elevated in lipid rafts under OS. In addition, OS increased the level of activated integrin α5 in lipid rafts through the regulation of membrane cholesterol and fluidity. Disruption of F-actin-based cytoskeleton and knockdown of caveolin-1 prevented the OS-induced integrin α5 translocation and activation. In vivo, integrin α5 activation and EC dysfunction were observed in the atheroprone areas of low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice, and knockdown of integrin α5 markedly attenuated EC dysfunction in partially ligated carotid arteries. Consistent with these findings, mice with haploinsufficency of integrin α5 exhibited a reduction of atherosclerotic lesions in the regions under atheroprone flow. The present study has revealed an integrin- and membrane lipid raft-dependent mechanotransduction mechanism by which atheroprone flow causes endothelial dysfunction.

  4. Transcranial Doppler blood flow measurement during cesarean section in two patients with cerebral vascular disease.

    Science.gov (United States)

    Smiley, R M; Ridley, D M; Hartmann, A; Ciliberto, C F; Baxi, L

    2002-07-01

    We present two cases of neurovascular disease in pregnancy in which transcranial Doppler was used to assess the status of the cerebral circulation during cesarean section under regional anesthesia. One woman had been found to have moyamoya disease, following a series of transient ischemic attacks during her first pregnancy, which ended in spontaneous abortion. On this occasion she was delivered by cesarean section under slowly-induced epidural anesthesia, using ephedrine to maintain the blood pressure, and transcranial Doppler revealed no change in signal in her left middle cerebral artery. Both mother and baby had an uneventful post natal course. The second case involved a primiparous woman with a large arteriovenous malformation that had been detected following generalized seizures, which were treated with valproic acid. Her cesarean section was conducted under spinal anesthesia, and her blood pressure maintained with ephedrine. Again transcranial Doppler revealed no change in signal in her middle cerebral artery during the procedure. We believe this is a potentially useful technique to monitor the cerebral circulation intraoperatively in the presence of cerebrovascular disease.

  5. Extra-long Float-zones Induced by Thermocapillary Flows

    Science.gov (United States)

    Chen, Yi-Ju; Steen, Paul H.

    1996-11-01

    A model problem is posed to study the influence of flow on the interfacial stability of a nearly cylindrical liquid bridge for lengths near its circumference (the Plateau-Rayleigh limit). Zero gravity is assumed. The flow is generated by a shear stress imposed on the deformable interface. The symmetry of the imposed stress mimics the thermocapillary effect induced on a float-zone by a ring heater (i.e. a full zone). Numerical solutions, complemented by a bifurcation analysis, show that bridges substantially longer than the Plateau-Rayleigh limit are possible. An interaction of the first two capillary instabilities through the stress-induced pressure gradient is responsible. Time-periodic standing waves are also predicted in certain parameter ranges. Motivation comes from extra-long float-zones observed in MEPHISTO space lab experiments (June 1994).

  6. Numerical study on multiphase flows induced by wall adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Myong, Hyon Kook [Kookmin Univ., Seoul (Korea, Republic of)

    2012-07-15

    The present paper presents a numerical study on multiphase flows induced by wall adhesion. The continuum surface force (CSF) model with the wall adhesion boundary condition model is used for calculating the surface tension force; this model is implemented in an in house solution code (PowerCFD). The present method (code) employs an unstructured cell centered method based on a conservative pressure based finite volume method with a volume capturing method (CICSAM) in a volume of fluid (VOF) scheme for phase interface capturing. The effects of wall adhesion are then numerically simulated by using the present method for a shallow pool of water located at the bottom of a cylindrical tank with no external forces such as gravity. Two different cases are computed, one it which the water wets the wall and one in which the water does not wet the wall. It is found that the present method efficiently simulates the surface tension dominant multiphase flows induced by wall adhesion.

  7. Low levels of the reverse transactivator fail to induce target transgene expression in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Nikenza Viceconte

    Full Text Available Hutchinson-Gilford progeria syndrome (HGPS is a genetic disease with multiple features that are suggestive of premature aging. Most patients with HGPS carry a mutation on one of their copies of the LMNA gene. The LMNA gene encodes the lamin A and lamin C proteins, which are the major proteins of the nuclear lamina. The organs of the cardiovascular system are amongst those that are most severely affected in HGPS, undergoing a progressive depletion of vascular smooth muscle cells, and most children with HGPS die in their early teens from cardio-vascular disease and other complications from atherosclerosis. In this study, we developed a transgenic mouse model based on the tet-ON system to increase the understanding of the molecular mechanisms leading to the most lethal aspect of HGPS. To induce the expression of the most common HGPS mutation, LMNA c.1824C>T; p.G608G, in the vascular smooth muscle cells of the aortic arch and thoracic aorta, we used the previously described reverse tetracycline-controlled transactivator, sm22α-rtTA. However, the expression of the reverse sm22α-transactivator was barely detectable in the arteries, and this low level of expression was not sufficient to induce the expression of the target human lamin A minigene. The results from this study are important because they suggest caution during the use of previously functional transgenic animal models and emphasize the importance of assessing transgene expression over time.

  8. Vulnerability Assessment of Rainfall-Induced Debris Flow

    Science.gov (United States)

    Lu, G. Y.; Wong, D. W.; Chiu, L. S.

    2006-05-01

    Debris flow is a common hazard triggered by large amount of rainfall over mountainous areas. A debris flow event results from a complex interaction between rainfall and topographical properties of watersheds. Heavy rainfall facilitates this process by increasing pore water pressure, seepage force and reducing effective stress of soils (normal stress carried by soil particles at the points of contact). Since debris flow events are closely related to topography and rainfall, the goal of this research is to assess debris flow vulnerability related to these two factors. Objectives of this research are to: (1) examine new spatial interpolation techniques to estimate high spatial rainfall data relevant to debris flows. (2) develop topographical factors using Geography Information System (GIS) and remote sensing (RS) approaches and (3) combine the estimated rainfall and topographical factors to assess the vulnerability of debris flow. We examined three spatial interpolation techniques: adaptive inversed distance weight (AIDW), simple kriging and spatial disaggregation using wind induced-topographic effect that incorporates gauge measurements, satellite remote sensing data (TRMM). The topographical factors are derived from high resolution digital elevation model (DEM), and adopt fuzzy-based topographical models proposed by Tseng (2004). Estimated rainfall and topographical factors are processed by self-organizing maps (SOM) to provide vulnerability assessment. To demonstrate our technique, rainfall data collected by 39 rain gauges in the central part of Taiwan during the passage of Typhoon Tori-Ji around July 29, 2001 were used. Results indicate that the proposed spatial interpolation methods outperform existing methods (i.e. kriging, inverse distance weight, and co-kriging methods). The vulnerability assessment of 187 debris flows watersheds in the study area will be presented. Keyword: Debris flow, spatial interpolation, adaptive inverse distance weight, TRMM, self

  9. Flow-induced structured phase in nonionic micellar solutions.

    Science.gov (United States)

    Cardiel, Joshua J; Tonggu, Lige; de la Iglesia, Pablo; Zhao, Ya; Pozzo, Danilo C; Wang, Liguo; Shen, Amy Q

    2013-12-17

    In this work, we consider the flow of a nonionic micellar solution (precursor) through an array of microposts, with focus on its microstructural and rheological evolution. The precursor contains polyoxyethylene(20) sorbitan monooleate (Tween-80) and cosurfactant monolaurin (ML). An irreversible flow-induced structured phase (NI-FISP) emerges after the nonionic precursor flows through the hexagonal micropost arrays, when subjected to strain rates ~10(4) s(-1) and strain ~10(3). NI-FISP consists of close-looped micellar bundles and multiconnected micellar networks as evidenced by transmission electron microscopy (TEM) and cryo-electron microscopy (cryo-EM). We also conduct small-angle neutron scattering (SANS) measurements in both precursor and NI-FISP to illustrate the structural transition. We propose a potential mechanism for the NI-FISP formation that relies on the micropost arrays and the flow kinematics in the microdevice to induce entropic fluctuations in the micellar solution. Finally, we show that the rheological variation from a viscous precursor solution to a viscoelastic micellar structured phase is associated with the structural evolution from the precursor to NI-FISP.

  10. Roughness induced flow separation in adverse pressure gradient

    Science.gov (United States)

    Joo, Jongwook; Emory, Mike; Bose, Sanjeeb; Medic, Gorazd; Sharma, Om

    2016-11-01

    Surface roughness does not only increase turbulent mixing, but also thickens boundary-layers, making flows more susceptible to separation. Detailed flow physics related to the separation is not understood well. Bammert and Milsch (1972) demonstrates a clear example of surface roughness induced separation under adverse pressure gradient. In the study, compressor cascades with NACA 65 airfoils are systematically roughened and the flow over suction surface gradually separates early as roughness increases. A set of Large-Eddy Simulations (LES) over the Bammert's case is investigated, since RANS simulations using roughness models suffer from capturing the separation. In the current study, surface roughness is represented in two different approaches; 1) Realistic rough surface represented by stochastically distributed hills and valleys are gridded and solved with unstructured finite volume method, 2) Using block-structured grid, surface roughness is gridded as a staggered array of 3D rectangles, in a similar way of the previous study for roughened low pressure turbine (GT2016-57912). The current LES's capture rich features of the flow phenomena, which will bring comprehensive understanding of the roughness induced separation. This collaboration is made through 2016 CTR Summer Program.

  11. Therapeutic effect of osteogenically induced adipose derived stem cells on vascular deprivation-induced osteonecrosis of the femoral head in rabbits

    Institute of Scientific and Technical Information of China (English)

    Abudusaimi Aimaiti; Yilixiati Saiwulaiti; Maimaitiming Saiyiti; WANG Yun-hai; CUI Lei; Aihemaitijiang Yusufu

    2011-01-01

    Objective: To explore the therapeutic effect of osteogenically induced adipose-derived stem cells (ADSCs) on vascular deprivation-induced osteonecrosis of the femoral head (ONFH) in rabbit model. Methods: Vascular deprivation-induced ONFH was established by intramuscular injection of methylprednisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation in adult New Zealand white rabbits. Eight weeks after the establishment of vascular deprivation-induced ONFH, animals were randomly divided into three equal groups. In Group A (control), no therapy was given. In Group B, core decompression was performed by drilling a hole (1.2 mm in diameter) from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter. In Group C, 1 ×107 osteogenically induced ADSCs were resuspended in 0.5 ml PBS, and then injected directly into the femoral head. Femoral head specimens were obtained at postoperative 8 weeks. The bone formation and three-dimensional microstructure of the femoral head was evaluated by micro-computed tomography scans (μ-CT). Immunohistochemical analysis was performed to detect the expression of osteocalcin. Angiogenesis and repair of the femoral head were observed histologically. Results: In trabecular bone at the proximal femur region, the trabecular volume was higher in Group C (130.70 mm3± 4.33 mm3) than that in Groups A (101.07 mm3±7.76 mm3) and B (107.89 mm3±8.68 mm3, P<0.01). Bone volume was significantly increased in Group C (40.09 mm3±6.35 mm3) than in Groups A (29.65 mm3±4.61 mm3) and B (31.80 mm3± 4.01 mm3, P<0.01). The trabecular number was higher in Groups C (1.58±0.25) than other two groups (1.15±0.18, 1.16± 0.21, P<0.01). Bone mineral density showed statistically significant difference between Groups C and A or B (375.38± 23.06) mg HA/ccm, vs (313.73 ±19.30) mg HA/ccm and (316.09± 16.45) mg HA/ccm, P<0.01). Histological examination indicated that there was more new bone formation in

  12. Flow induced vibration studies on PFBR control plug components

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, V., E-mail: prakash@igcar.gov.in [Fast Reactor Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamilnadu (India); Kumar, P. Anup; Anandaraj, M.; Thirumalai, M.; Anandbabu, C.; Rajan, K.K. [Fast Reactor Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamilnadu (India)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer Flow induced vibration studies on Prototype Fast Breeder Reactor control plug model carried out. Black-Right-Pointing-Pointer Velocity similitude was followed for the study. Black-Right-Pointing-Pointer Frequencies and amplitude of vibrations of various control plug components measured. Black-Right-Pointing-Pointer Overall values of vibration are well within permissible limits. - Abstract: The construction of Prototype Fast Breeder Reactor (PFBR), a 500 MWe liquid sodium cooled reactor, is in progress at Kalpakkam in India. Control plug (CP) is located right above the core subassemblies in the hot pool. Control plug is an important component as many of the critical reactor parameters are sensed and controlled by the components housed in the control plug assembly. In PFBR primary circuit, components are basically thin walled, slender shells with diameter to thickness ratio ranging from 100 to 650. These components are prone to flow induced vibrations. The existence of free liquid (sodium) surfaces, which is the source of sloshing phenomenon and the operation of primary sodium pump in the primary pool are other potential sources of vibration of reactor components. Control plug is a hollow cylindrical shell structure and provides passages and support for 12 absorber rod drive mechanisms (ARDM) which consists of 9 control and safety rods and 3 diverse safety rods, 210 thermo wells to measure the sodium temperature at the exit of various fuel subassemblies, three failed fuel localization modules (FFLM) and acoustic detectors. It consists of a core cover plate (CCP), which forms the bottom end, two intermediate sup