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  1. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C;

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects...... without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile...

  2. A gene-centric study of common carotid artery remodelling

    NARCIS (Netherlands)

    Harrison, Seamus C.; Zabaneh, Delilah; Asselbergs, Folkert W.; Drenos, Fotios; Jones, Gregory T.; Shah, Sonia; Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Gigante, Bruna; Holewijn, Suzanne; De Graaf, Jacqueline; Vermeulen, Sita; Folkersen, Lasse; van Rij, Andre M.; Baldassarre, Damiano; Veglia, Fabrizio; Talmud, Philippa J.; Deanfield, John E.; Agu, Obi; Kivimaki, Mika; Kumari, Meena; Bown, Matthew J.; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Franco-Cereceda, Anders; Giral, Philippe; Mannarino, Elmo; Silveira, Angela; Syvanen, Ann-Christine; de Borst, Gert J.; van der Graaf, Yolanda; de Faire, Ulf; Baas, Annette F.; Blankensteijn, Jan D.; Wareham, Nicholas J.; Fowkes, Gerry; Tzoulaki, Ionna; Price, Jacqueline F.; Tremoli, Elena; Hingorani, Aroon D.; Eriksson, Per; Hamsten, Anders; Humphries, Steve E.

    2013-01-01

    Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IM

  3. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Jane A. Leopold

    2016-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype.

  4. The redox state of transglutaminase 2 controls arterial remodeling

    DEFF Research Database (Denmark)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon;

    2011-01-01

    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, ...

  5. Pulmonary arterial remodeling revealed by microfocal x-ray tomography

    Science.gov (United States)

    Karau, Kelly L.; Molthen, Robert C.; Johnson, Roger H.; Dhyani, Anita H.; Haworth, Steven T.; Dawson, Christopher A.

    2001-05-01

    Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This 'self-consistency' property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns.

  6. Mechanisms of arterial remodeling: lessons from genetic diseases

    Directory of Open Access Journals (Sweden)

    Bernard eVan Varik

    2012-12-01

    Full Text Available Vascular disease is still the leading cause of morbidity and mortality in the Western world, and the primary cause of myocardial infarction, stroke, and ischemia. The biology of vascular disease is complex and still poorly understood in terms of causes and consequences. Vascular function is determined by structural and functional properties of the arterial vascular wall. Arterial stiffness, that is a pathological alteration of the vascular wall, ultimately results in target-organ damage and increased mortality. Arterial remodeling is accelerated under conditions that adversely affect the balance between arterial function and structure such as hypertension, atherosclerosis, diabetes mellitus, chronic kidney disease, inflammatory disease, lifestyle aspects (smoking, drugs (vitamin K antagonists and genetic abnormalities (e.g. pseudoxanthoma elasticum, Marfan’s disease. The aim of this review is to provide an overview of the complex mechanisms and different factors that underlie arterial remodeling, learning from single gene defect diseases like PXE, and PXE-like, Marfan’s disease and Keutel syndrome in vascular remodeling.

  7. Remodelling of the microarchitecture of resistance arteries in cardiovascular diseases

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Brewer, Jonathan R.; Leurgans, Thomas;

    in comparison to other well-studied microvascular beds (e.g. rat mesentery). In the future we aim to compare the microarchitecture of small resistance arteries from parietal pericardial biopsies between patients with and without (treated) hypertension, diabetes and/or ischemic heart disease. 1. Buus, N.H., et...... is largely unknown, and the presented project aims to investigate this. Innovative multiphoton excitation microscopy will be applied on live (vital), isolated, cannulated and pressurized arteries from parietal pericardial biopsies obtained during open cardiac surgery (coronary artery bypass grafting......Small resistance artery structure is an independent predictor of cardiovascular events in essential hypertension [1, 2] and diabetes (types I and II) [3, 4]. In particular, the media-to-lumen ratio (M:L) is predictive of cardiovascular events. The exact nature of this resistance artery remodeling...

  8. Efficacy of losartan for improving insulin resistance and vascular remodeling in hemodialysis patients.

    Science.gov (United States)

    Sun, Fang; Song, Yan; Liu, Jing; Ma, Li-Jie; Shen, Yang; Huang, Jing; Zhou, Yi-Lun

    2016-01-01

    Insulin resistance and vascular remodeling are prevalent and predict cardiovascular mortality in hemodialysis patients. Angiotensin II (Ang II) may be involved in both pathogenesis. In the present study, we investigated the effects of the Ang II receptor blocker losartan on insulin resistance, arterial stiffness, and carotid artery structure in hemodialysis patients. Seventy-two hemodialysis patients were randomly assigned to receive either losartan 50 mg qd (n = 36) or β-blocker bisoprolol 5 mg qd (n = 36). At the start and at month 12, ambulatory blood pressure (BP) monitoring, aortic pulse wave velocity (PWV) measurements, and carotid artery ultrasound were performed, and homeostasis model assessment index of insulin resistance (HOMA-IR) was determined. During the study period, bioimpedance method was used to evaluate volume status every 3 months. Home-monitored BPs were measured at least monthly. Ambulatory BP decreased significantly and similarly by either losartan or bisoprolol. Decreases in PWVs in losartan group at the end of month 12 were significantly greater than changes in PWV in bisoprolol group (0.9 ± 0.3 vs. 0.4 ± 0.5 m/s, P = 0.021). Common carotid artery intima-media cross-sectional area decreased significantly only in patients treated with losartan (20.3 ± 4.9 vs. 19.1 ± 5.1 mm(2) , P = 0.001), and HOMA-IR was also reduced in losartan group only (1.9 ± 1.0 vs. 1.7 ± 0.8, P = 0.003). Multiple regression analysis showed significant correlations between changes in PWV and changes in HOMA-IR. With comparable BP-lowering efficacy, losartan achieved better improvement in insulin sensitivity, arterial stiffness, and carotid artery hypertrophy in hemodialysis patients. The regression of arterial stiffness may be in part through attenuation in insulin resistance.

  9. Relationship between coronary arterial remodeling and clinical presentation

    Institute of Scientific and Technical Information of China (English)

    杨震坤; 沈卫峰; 张大东

    2003-01-01

    Objective To examine the relationship between coronary arterial remodeling and clinical presentation. Methods A total of 34 patients with acute (10 with recent myocardial infarction and 24 with unstable angina) and 26 with stable (8 with old myocardial infarction and 18 with stable angina) coronary syndrome underwent intravascular ultrasound (IVUS) before intervention. Target lesions were classified as soft or hard plaques. Q uantitative measurements of cross-sectional area (CSA) of external elastic memb rane (EEM), lumen and plaque were performed at the lesion site and at the proxim al and distal reference sites. Remodeling index (RI) was expressed by the ratio of EEM CSA at the lesion site to the mean EEM CSA of both proximal and distal r eference sites. Positive remodeling was defined as RI>1.05 and negative remode ling as RI<0.95. Results Soft plaque was observed more frequently in acute than in stable coronary syndrome (59% vs 31%), whereas hard plaque was more common in stable coronary syndrome (69% vs 41%) (P=0.03). The EEM CSA (15.11±2.89 mm2 vs 13.25±3.10 mm2, P=0.019) and plaque CSA (10.83±2.62 mm2 vs 9.30±2.84 mm 2, P =0.035) were significantly greater at target lesions in patients with acute r ather than stable coronary syndrome, while lumen CSA and percent area stenosis w ere similar in both groups. RI was significantly higher (1.08±0.16 vs 0.95 ±0.14, P=0.002) and positive remodeling was more frequent in acute corona ry syndrome (53% vs 23%, P=0.019), whereas negative remodeling was more com mon in stable coronary syndrome (58% vs 24%, P=0.007). Conclusions The study indicates that clinical characteristics of patients with coronary artery disease depend largely upon underlying types of coronary arterial remodeling .

  10. Pulmonary arterial remodeling in chronic obstructive pulmonary disease is lobe dependent.

    Science.gov (United States)

    Wrobel, Jeremy P; McLean, Catriona A; Thompson, Bruce R; Stuart-Andrews, Christopher R; Paul, Eldho; Snell, Gregory I; Williams, Trevor J

    2013-09-01

    Abstract Pulmonary arterial remodeling has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD), but it is not known whether lobar heterogeneity of remodeling occurs. Furthermore, the relationship between pulmonary hypertension (PH) and pulmonary arterial remodeling in COPD has not been established. Muscular pulmonary arterial remodeling in arteries 0.10-0.25 mm in diameter was assessed in COPD-explanted lungs and autopsy controls. Remodeling was quantified as the percentage wall thickness to vessel diameter (%WT) using digital image analysis. Repeat measures mixed-effects remodeling for %WT was performed according to lobar origin (upper and lower), muscular pulmonary arterial size (small, medium, and large), and echocardiography-based pulmonary arterial pressure (no PH, mild PH, and moderate-to-severe PH). Lobar perfusion and emphysema indices were determined from ventilation-perfusion and computed tomography scans, respectively. Overall, %WT was greater in 42 subjects with COPD than in 5 control subjects ([Formula: see text]). Within the COPD group, %WT was greater in the upper lobes ([Formula: see text]) and in the small muscular pulmonary arteries ([Formula: see text]). Lobar differences were most pronounced in medium and large arteries. Lobar emphysema index was not associated with arterial remodeling. However, there was a significant positive relationship between the lobar perfusion index and pulmonary arterial remodeling ([Formula: see text]). The presence of PH on echocardiography showed only a trend to a small effect on lower lobe remodeling. The pattern of pulmonary arterial remodeling in COPD is complicated and lobe dependent. Differences in regional blood flow partially account for the lobar heterogeneity of pulmonary arterial remodeling in COPD. PMID:24618551

  11. Tissue remodeling of rat pulmonary arteries in recovery from hypoxic hypertension

    OpenAIRE

    Li, Zhuangjie; Huang, Wei; Jiang, Zong Lai; Gregersen, Hans; Fung, Yuan-Cheng

    2004-01-01

    The reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing is well known, but little has been said about the recovery of the arterial wall when the blood pressure is lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thickness...

  12. Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture.

    Science.gov (United States)

    Xiao, Yangming; Liu, Qin; Han, Hai-Chao

    2016-09-01

    Artery buckling alters the fluid shear stress and wall stress in the artery but its temporal effect on vascular wall remodeling is poorly understood. The purpose of this study was to investigate the early effect of artery buckling on endothelial nitric oxide synthase (eNOS) expression and extracellular matrix remodeling. Bilateral porcine carotid arteries were maintained in an ex vivo organ culture system with and without buckling while under the same physiological pressure and flow rate for 3-7 days. Matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin, elastin, collagen I, III and IV, tissue inhibitor of metalloproteinase-2 (TIMP-2), and eNOS were determined using Western blotting and immunohistochemistry. Our results showed that MMP-2 expression level was significantly higher in buckled arteries than in the controls and higher at the inner curve than at the outer curve of buckled arteries, while collagen IV content showed an opposite trend, suggesting that artery buckling increased MMP-2 expression and collagen IV degradation in a site-specific fashion. However, no differences for MMP-9, fibronectin, elastin, collagen I, III, and TIMP-2 were observed among the outer and inner curve sides of buckled arteries and straight controls. Additionally, eNOS expression was significantly decreased in buckled arteries. These results suggest that artery buckling triggers uneven wall remodeling that could lead to development of tortuous arteries. PMID:26913855

  13. Vascular-Leukocyte Interactions : Mechanisms of Human Decidual Spiral Artery Remodeling in Vitro

    OpenAIRE

    Hazan, Aleah D.; Smith, Samantha D.; Jones, Rebecca L; Whittle, Wendy; Lye, Stephen J.; Dunk, Caroline E.

    2010-01-01

    Transformation of uterine spiral arteries is critical for healthy human pregnancy. We recently proposed a role for maternal leukocytes in decidual spiral artery remodeling and suggested that matrix metalloprotease (MMP) activity contributed to the destruction of the arterial wall. In the current study we used our first trimester placental-decidual co-culture (PDC) model to define the temporal relationship and test the mechanistic aspects of this process. PDC experiments were assessed by image...

  14. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    Science.gov (United States)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  15. Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

    OpenAIRE

    Kurtz, Baptiste; Thibault, Helene B.; Raher, Michael J.; Popovich, John R.; Cawley, Sharon; Atochin, Dmitriy N.; Hayton, Sarah; Shakartzi, Hannah R.; Paul L Huang; Bloch, Kenneth D.; Buys, Emmanuel; Scherrer-Crosbie, Marielle

    2011-01-01

    Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat di...

  16. Molecular analysis of arterial remodeling: a novel application of infrared imaging

    Science.gov (United States)

    Herman, Brad C.; Kundi, Rishi; Yamanouchi, Dai; Kent, K. Craig; Liu, Bo; Pleshko, Nancy

    2009-02-01

    Arterial remodeling, i.e. changes in size and/or structure of arteries, plays an important role in vascular disease. Conflicting findings have been reported as to whether an abundance of collagen causes inward or outward remodeling, phenomena that result in either a smaller or larger lumen, respectively. We hypothesize that the amount, type and quality of collagen influence the remodeling response. Here, we create mechanical injury to the rat carotid artery using a balloon catheter, and this leads to inward remodeling. Treatment of the artery with Connective Tissue Growth Factor (CTGF) causes outward remodeling. We investigated the arterial composition in injured CTGF-treated and non-CTGF-treated and sham CTGF-treated and non-CTGF treated arteries 14 days post-injury (n = 7-8 per group) using infrared imaging. A Perkin Elmer Spotlight Spectrum 300 FT-IR microscope was used for data collection. Cross-sections of paraffinembedded arteries were scanned at 2 cm-1 spectral resolution with spatial resolution of 6.25 μm/pixel, and data analyzed using Malvern Instruments ISys 5.0. Post-injury, we found a nearly 50% reduction in the average 1338/AM2 area ratio (correlated to collagen helical integrity). The most dramatic change was a 600% increase in the 1660/1690 peak height ratio, which has previously been related to collagen crosslink maturity. In all cases, CTGF treatment resulted in the observed changes in peak parameters normalized back to control values. Overall, these preliminary studies demonstrate that infrared imaging can provide insight into the underlying molecular changes that contribute to arterial disease.

  17. Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow.

    Science.gov (United States)

    Li, Xiaohui; Du, Junbao; Jin, Hongfang; Geng, Bin; Tang, Chaoshu

    2008-11-01

    This study aimed to explore the effect of sodium hydrosulfide (NaHS) on pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham + NaHS (an H2S donor) group, and shunt + NaHS group. After 11 weeks of shunting, mean pulmonary artery pressure (MPAP), relative median area (RMA) of pulmonary arteries, H2S concentration in lung tissues, plasma endothelin-1 (ET-1) levels, and ET-1 mRNA in lung tissues were investigated. Collagen I and collagen III were evaluated by immunohistochemistry. Hydroxyproline assay and Sirius-red staining were performed. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 11 weeks of shunting, rats showed a significant pulmonary hypertension and pulmonary artery collagen remodeling in association with a decrease in lung tissue H2S content. After NaHS treatment for 11 weeks, lung tissue H(2)S content was increased, whereas MPAP was attenuated and RMA was reduced. Meanwhile, pulmonary artery collagen I and collagen III protein expressions of intra-acinar pulmonary arteries were inhibited, but MMP-13/TIMP-1 ratio was augmented with a decreased plasma ET-1 content and lung tissue ET-1mRNA and CTGF expressions. The downregulation of H(2)S is involved in the development of pulmonary artery collagen remodeling induced by high pulmonary blood flow.

  18. Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling

    Directory of Open Access Journals (Sweden)

    Kevin Retailleau

    2015-11-01

    Full Text Available The mechanically activated non-selective cation channel Piezo1 is a determinant of vascular architecture during early development. Piezo1-deficient embryos die at midgestation with disorganized blood vessels. However, the role of stretch-activated ion channels (SACs in arterial smooth muscle cells in the adult remains unknown. Here, we show that Piezo1 is highly expressed in myocytes of small-diameter arteries and that smooth-muscle-specific Piezo1 deletion fully impairs SAC activity. While Piezo1 is dispensable for the arterial myogenic tone, it is involved in the structural remodeling of small arteries. Increased Piezo1 opening has a trophic effect on resistance arteries, influencing both diameter and wall thickness in hypertension. Piezo1 mediates a rise in cytosolic calcium and stimulates activity of transglutaminases, cross-linking enzymes required for the remodeling of small arteries. In conclusion, we have established the connection between an early mechanosensitive process, involving Piezo1 in smooth muscle cells, and a clinically relevant arterial remodeling.

  19. Computer Simulation of the Mechanical Behaviour of Implanted Biodegradable Stents in a Remodelling Artery

    Science.gov (United States)

    Boland, Enda L.; Grogan, James A.; Conway, Claire; McHugh, Peter E.

    2016-04-01

    Coronary stents have revolutionised the treatment of coronary artery disease. While coronary artery stenting is now relatively mature, significant scientific and technological challenges still remain. One of the most fertile technological growth areas is biodegradable stents; here, there is the possibility to generate stents that will break down in the body once the initial necessary scaffolding period is past (6-12 months) (Grogan et al. in Acta Biomater 7:3523, 2011) and when the artery has remodelled (including the formation of neo-intima). A stent angioplasty computational test-bed has been developed by the authors, based on the Abaqus software (DS-SIMULIA, USA), capable of simulating stent tracking, balloon expansion, recoil and in vivo loading in a atherosclerotic artery model. Additionally, a surface corrosion model to simulate uniform and pitting corrosion of biodegradable stents and a representation of the active response of the arterial tissue following stent implantation, i.e. neointimal remodelling, has been developed. The arterial neointimal remodelling simulations with biodegradable stent corrosion demonstrate that the development of new arterial tissue around the stent struts has a substantial effect on the mechanical behaviour of degrading stents.

  20. The impact of exercise training on conduit artery wall thickness and remodeling in chronic heart failure patients

    NARCIS (Netherlands)

    Maiorana, A.J.; Naylor, L.H.; Exterkate, A.; Swart, A.; Thijssen, D.H.J.; Lam, K.; O'Driscoll, G.; Green, D.J.

    2011-01-01

    Exercise training is an important adjunct to medical therapy in chronic heart failure, but the extent to which exercise impacts on conduit artery remodeling is unknown. The aim of this study was to evaluate the impact of aerobic and resistance exercise training modalities on arterial remodeling in p

  1. Micro-CT Technique Is Well Suited for Documentation of Remodeling Processes in Murine Carotid Arteries

    OpenAIRE

    Christoph Schürmann; Felix Gremse; Hanjoong Jo; Fabian Kiessling; Brandes, Ralf P.

    2015-01-01

    Background: The pathomechanisms of atherosclerosis and vascular remodelling are under intense research. Only a few in vivo tools to study these processes longitudinally in animal experiments are available. Here, we evaluated the potential of micro-CT technology. Methods: Lumen areas of the common carotid arteries (CCA) in the ApoE-/- partial carotid artery ligation mouse model were compared between in vivo and ex vivo micro-CT technique and serial histology in a total of 28 animals. AuroVi...

  2. Uterine artery remodeling in pseudopregnancy is comparable to that in early pregnancy.

    NARCIS (Netherlands)

    Heijden, O.W. van der; Essers, Y.P.; Spaanderman, M.E.A.; Mey, J.G. de; Eys, G. van; Peeters, L.L.

    2005-01-01

    During pregnancy, the lumenal diameter and wall mass of the uterine artery (UA) increase, most likely in response to the increased hemodynamic strain resulting from the chronically elevated uterine blood flow (UBF). In this remodeling process, the phenotype of vascular smooth-muscle cells (VSMC) is

  3. β Integrins Mediate FAK Y397 Autophosphorylation of Resistance Arteries during Eutrophic Inward Remodeling in Hypertension

    OpenAIRE

    Heerkens, Egidius H.J; Quinn, Lisa; Withers, Sarah B.; Heagerty, Anthony M

    2014-01-01

    Human essential hypertension is characterized by eutrophic inward remodeling of the resistance arteries with little evidence of hypertrophy. Upregulation of αVβ3 integrin is crucial during this process. In order to investigate the role of focal adhesion kinase (FAK) activation in this process, the level of FAK Y397 autophosphorylation was studied in small blood vessels from young TGR(mRen2)27 animals as blood pressure rose and eutrophic inward remodeling took place. Between weeks 4 and 5, thi...

  4. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  5. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progeni

  6. Relaxing effect of insulin in renal arteries from diabetic rats

    DEFF Research Database (Denmark)

    Torffvit, O; Edvinsson, L

    1999-01-01

    -treated streptozotocine diabetic rats with diabetes for 50 days were compared with 15 weight-matched control rats. The contractile responses to 60 mM K+ and 10(-4) M noradrenaline, and the insulin- (0.8-6.4 I.U./ml) induced relaxation of vessels precontracted with noradrenaline, were similar in diabetic and control rats....... There was a tendency towards greater relaxation in diabetic (71%) than in control rats (54%). Nw-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) given before noradrenaline tended to attenuate the insulin-induced relaxation, while addition of L-arginine (10(-6) M) to L-NAME attenuated the relaxation in diabetic...... in control rats in varying doses between 2 x 10(-6) and 2 x 10(-4) M. In the highest concentration it made no difference whether insulin was given or not and there was a similar relaxing effect in diabetic and control arteries. In conclusion, the present study showed that insulin per se has a relaxing effect...

  7. Remodeling lipid metabolism and improving insulin responsiveness in human primary myotubes.

    Directory of Open Access Journals (Sweden)

    Lauren M Sparks

    Full Text Available OBJECTIVE: Disturbances in lipid metabolism are strongly associated with insulin resistance and type 2 diabetes (T2D. We hypothesized that activation of cAMP/PKA and calcium signaling pathways in cultured human myotubes would provide further insight into regulation of lipid storage, lipolysis, lipid oxidation and insulin responsiveness. METHODS: Human myoblasts were isolated from vastus lateralis, purified, cultured and differentiated into myotubes. All cells were incubated with palmitate during differentiation. Treatment cells were pulsed 1 hour each day with forskolin and ionomycin (PFI during the final 3 days of differentiation to activate the cAMP/PKA and calcium signaling pathways. Control cells were not pulsed (control. Mitochondrial content, (14C lipid oxidation and storage were measured, as well as lipolysis and insulin-stimulated glycogen storage. Myotubes were stained for lipids and gene expression measured. RESULTS: PFI increased oxidation of oleate and palmitate to CO(2 (p<0.001, isoproterenol-stimulated lipolysis (p = 0.01, triacylglycerol (TAG storage (p<0.05 and mitochondrial DNA copy number (p = 0.01 and related enzyme activities. Candidate gene and microarray analysis revealed increased expression of genes involved in lipolysis, TAG synthesis and mitochondrial biogenesis. PFI increased the organization of lipid droplets along the myofibrillar apparatus. These changes in lipid metabolism were associated with an increase in insulin-mediated glycogen storage (p<0.001. CONCLUSIONS: Activation of cAMP/PKA and calcium signaling pathways in myotubes induces a remodeling of lipid droplets and functional changes in lipid metabolism. These results provide a novel pharmacological approach to promote lipid metabolism and improve insulin responsiveness in myotubes, which may be of therapeutic importance for obesity and type 2 diabetes.

  8. 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension.

    Science.gov (United States)

    Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L; Falck, John R; Capdevila, Jorge H; Schwartzman, Michal L

    2013-09-01

    20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5α-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14(-/-) mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 μm) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12-20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 μm; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID

  9. Time course of arterial remodelling in diameter and wall thickness above and below the lesion after a spinal cord injury

    NARCIS (Netherlands)

    Thijssen, D.H.J.; Groot, P.C. de; Bogerd, A. van den; Veltmeijer, M.; Cable, N.T.; Green, D.J.; Hopman, M.T.E.

    2012-01-01

    Physical inactivity in response to a spinal cord injury (SCI) represents a potent stimulus for conduit artery remodelling. Changes in conduit artery characteristics may be induced by the local effects of denervation (and consequent extreme inactivity below the level of the lesion), and also by syste

  10. Time course of arterial remodelling in diameter and wall thickness above and below the lesion after a spinal cord injury

    OpenAIRE

    Dick H J Thijssen; de Groot, Patricia C. E.; van den Bogerd, Arne; Veltmeijer, Matthijs; Cable, N. Timothy; Green, Daniel J.; Hopman, Maria T. E.

    2012-01-01

    Physical inactivity in response to a spinal cord injury (SCI) represents a potent stimulus for conduit artery remodelling. Changes in conduit artery characteristics may be induced by the local effects of denervation (and consequent extreme inactivity below the level of the lesion), and also by systemic adaptations due to whole body inactivity. Therefore, we assessed the time course of carotid (i.e. above lesion) and common femoral artery (i.e. below lesion) lumen diameter and wall thickness a...

  11. Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T;

    2012-01-01

    )-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP......)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10±1 × 10(3) to 17±2 × 10(3) μm(2); 6 weeks: 13±2 × 10(3) to 24±3 × 10(3) μm(2)). After 3, but not 6, weeks of hypertension, the arterial diameter...... was increased (Ø: 385±13 to 463±14 μm). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 × 10(3)±1 × 10(3) μm(2)). The diameter of the HF arteries of normotensive rats increased (Ø: 463±22 μm) but no expansion occurred in the HF arteries of hypertensive rats (Ø: 471±16 μm). MrA from SOL...

  12. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee.

    Science.gov (United States)

    Pijnenborg, R; Vercruysse, L; Carter, A M

    2011-05-01

    Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned. The availability of two well-documented pregnant chimpanzee uteri in the Hubrecht Collection (Museum für Naturkunde, Berlin) allowed us to evaluate the extent of trophoblast invasion in this species. By adjusting currently used protocols, we obtained successful immunohistochemical staining for cytokeratin and α-actin, as well as Ulex europaeus agglutinin 1 (UEA1) lectin staining, in this archival material. In both specimens interstitial trophoblast invasion had occurred in both decidua and myometrium. Because of a lack of published data on fetal growth for this species, fetal sizes (7cm and 13cm) could not be strictly related to gestational ages and thus be compared with the time-course of human trophoblast invasion. However, since the earlier specimen did not show any endovascular trophoblast invasion in spiral arteries - in contrast to pregnant human uteri with equivalent fetal sizes - endovascular migration seems to begin at a different gestational age in the chimpanzee. In the later specimen endovascular trophoblast was associated with spiral artery remodelling in the inner myometrium, and this invasion was extended to include a radial artery, which at that stage still showed relatively intact vascular smooth muscle and elastic lamina. We conclude that invasion depth and spiral artery remodelling are basically similar in chimpanzees and humans, although the seemingly different time of onset may have implications for uteroplacental oxygen supply and fetal development.

  13. Micro-CT Technique Is Well Suited for Documentation of Remodeling Processes in Murine Carotid Arteries.

    Directory of Open Access Journals (Sweden)

    Christoph Schürmann

    Full Text Available The pathomechanisms of atherosclerosis and vascular remodelling are under intense research. Only a few in vivo tools to study these processes longitudinally in animal experiments are available. Here, we evaluated the potential of micro-CT technology.Lumen areas of the common carotid arteries (CCA in the ApoE-/- partial carotid artery ligation mouse model were compared between in vivo and ex vivo micro-CT technique and serial histology in a total of 28 animals. AuroVist-15 nm nanoparticles were used as in vivo blood pool contrast agent in a Skyscan 1176 micro-CT at resolution of 18 μmeter voxel size and a mean x-ray dose of 0.5 Gy. For ex vivo imaging, animals were perfused with MicroFil and imaged at 9 μmeter voxel size. Lumen area was evaluated at postoperative days 7, 14, and 28 first by micro-CT followed by histology.In vivo micro-CT and histology revealed lumen loss starting at day 14. The lumen profile highly correlated (r = 0.79, P<0.0001 between this two methods but absolute lumen values obtained by histology were lower than those obtained by micro-CT. Comparison of in vivo and ex vivo micro-CT imaging revealed excellent correlation (r = 0.83, P<0.01. Post mortem micro-CT yielded a higher resolution than in vivo micro-CT but there was no statistical difference of lumen measurements in the partial carotid artery ligation model.These data demonstrate that in vivo micro-CT is a feasible and accurate technique with low animal stress to image remodeling processes in the murine carotid artery.

  14. Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2015-01-01

    This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

  15. Effect of L-Arginine on Pulmonary Artery Smooth Muscle Cell Apoptosis in Rats with Hypoxic Pulmonary Vascular Structural Remodeling

    Institute of Scientific and Technical Information of China (English)

    Ingrid Karmane SUMOU; Jun-Bao DU; Bing WEI; Chun-Yu ZHANG; Jian-Guang QI; Chao-Shu TANG

    2006-01-01

    This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatebiotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

  16. Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.

    Science.gov (United States)

    Elajami, Tarec K; Colas, Romain A; Dalli, Jesmond; Chiang, Nan; Serhan, Charles N; Welty, Francine K

    2016-08-01

    Inflammation in arterial walls leads to coronary artery disease (CAD). Because specialized proresolving lipid mediators (SPMs; lipoxins, resolvins, and protectins) stimulate resolution of inflammation in animal models, we tested whether n-3 fatty acids impact SPM profiles in patients with CAD and promote clot remodeling. Six patients with stable CAD were randomly assigned to either treatment with daily 3.36 g Lovaza for 1 yr or without. Targeted lipid mediator-metabololipidomics showed that both groups had absence of resolvin D1 (RvD1), RvD2, RvD3, RvD5 and resolvin E1-all of which are present in healthy patients. Those not taking Lovaza had an absence of aspirin-triggered resolvin D3 (AT-RvD3) and aspirin-triggered lipoxin B4 (AT-LXB4). Lovaza treatment restored AT-RvD3 and AT-LXB4 and gave levels of RvD6 and aspirin-triggered protectin D1 (AT-PD1) twice as high (resolvin E2 ∼5 fold) as well as lower prostaglandins. Principal component analysis indicated positive relationships for patients with CAD who were receiving Lovaza with increased AT-RvD3, RvD6, AT-PD1, and AT-LXB4 SPMs identified in Lovaza-treated patients with CAD enhanced ∼50% at 1 nM macrophage uptake of blood clots. These results indicate that patients with CAD have lower levels and/or absence of specific SPMs that were restored with Lovaza; these SPMs promote macrophage phagocytosis of blood clots. Together, they suggest that low vascular SPMs may enable progression of chronic vascular inflammation predisposing to coronary atherosclerosis and to thrombosis.-Elajami, T. K., Colas, R. A., Dalli, J., Chiang, N., Serhan, C. N., Welty, F. K. Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling. PMID:27121596

  17. Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats

    Directory of Open Access Journals (Sweden)

    Onyia Jude E

    2010-05-01

    Full Text Available Abstract Objectives Endothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi on endothelial function and mechanical remodeling. Methods The Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using an ex-vivo isovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS, α-adrenoceptor, matrix metalloproteinase 9 (MMP9, and elastase were evaluated. Results Endothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6 mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats. Conclusion The endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties.

  18. Double-balloon remodeling for coil embolization of a primitive trigeminal artery variant aneurysm. A case report.

    Science.gov (United States)

    Takigawa, Tomoji; Suzuki, Kensuke; Sugiura, Yoshiki; Suzuki, Ryotaro; Takano, Issei; Shimizu, Nobuyuki; Tanaka, Yoshihiro; Hyodo, Akio

    2014-01-01

    Here we describe the case of a patient with a wide-necked unruptured aneurysm arising at origin of a persistent primitive trigeminal artery (PTA) variant from the right internal carotid artery (ICA), supplying the territory of the right superior cerebellar artery and the anterior inferior cerebellar artery. To preserve the ICA and the PTA variant, coil embolization of the aneurysm was performed using a double-balloon remodeling technique (HyperForm™ and HyperGlide™ Occlusion Balloon Systems; ev3 Endovascular Inc., Irvine, CA, USA). The association of a PTA variant with an aneurysm is very rare. To our knowledge, this is the first description of the use of coil embolization using double-balloon remodeling to treat a PTA variant aneurysm. This technique permits complete embolization and reduces the risk of cerebral and cerebellar ischemia. PMID:24976091

  19. Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Theilade, Simone; Hansen, Tine Willum;

    2014-01-01

    AIMS: To investigate the relationship between arterial stiffness and insulin treatment mode [continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)] in type 1 diabetes patients. METHODS: Cross-sectional study, from 2009 to 2011, including 601 Caucasian type 1...

  20. Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases

    International Nuclear Information System (INIS)

    Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial

  1. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned. The avai......Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned...... muscle and elastic lamina. We conclude that invasion depth and spiral artery remodelling are basically similar in chimpanzees and humans, although the seemingly different time of onset may have implications for uteroplacental oxygen supply and fetal development....

  2. Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Xiang-Rong Zuo

    Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

  3. Leukemia Inhibitory Factor (LIF) Inhibition during Mid-Gestation Impairs Trophoblast Invasion and Spiral Artery Remodelling during Pregnancy in Mice.

    Science.gov (United States)

    Winship, Amy; Correia, Jeanne; Zhang, Jian-Guo; Nicola, Nicos A; Dimitriadis, Evdokia

    2015-01-01

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Trophoblast cell proliferation, migration and invasion into the endometrium are fundamental events in the initiation of placentation. Leukemia inhibitory factor (LIF) has been shown to promote trophoblast invasion in vitro, however its precise role in trophoblast invasion in vivo is unknown. We hypothesized that LIF would be required for normal trophoblast invasion and spiral artery remodeling in mice. Both LIF and its receptor (LIFRα) co-localized with cytokeratin-positive invasive endovascular extravillous trophoblasts (EVT) in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via administration of our unique LIFRα antagonist, PEGLA, resulted in abnormal trophoblast invasion and impaired spiral artery remodeling compared to PEG control. PEGLA-treated mouse decidual vessels were characterized by retention of α-smooth muscle actin (αSMA)-positive vascular smooth muscle cells (VSMCs), while PEG control decidual vessels were remodelled by cytokeratin-positive trophoblasts. LIF blockade did not alter F4/80-positive decidual macrophage numbers between treatment groups, but resulted in down-regulation of decidual transcript levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10), which are important immune cell activation factors that promote spiral artery remodeling during pregnancy. Our data suggest that LIF plays an important role in trophoblast invasion in vivo and may facilitate trophoblast-decidual-immune cell cross talk to enable adequate spiral artery remodeling. PMID:26479247

  4. Leukemia Inhibitory Factor (LIF Inhibition during Mid-Gestation Impairs Trophoblast Invasion and Spiral Artery Remodelling during Pregnancy in Mice.

    Directory of Open Access Journals (Sweden)

    Amy Winship

    Full Text Available The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Trophoblast cell proliferation, migration and invasion into the endometrium are fundamental events in the initiation of placentation. Leukemia inhibitory factor (LIF has been shown to promote trophoblast invasion in vitro, however its precise role in trophoblast invasion in vivo is unknown. We hypothesized that LIF would be required for normal trophoblast invasion and spiral artery remodeling in mice. Both LIF and its receptor (LIFRα co-localized with cytokeratin-positive invasive endovascular extravillous trophoblasts (EVT in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via administration of our unique LIFRα antagonist, PEGLA, resulted in abnormal trophoblast invasion and impaired spiral artery remodeling compared to PEG control. PEGLA-treated mouse decidual vessels were characterized by retention of α-smooth muscle actin (αSMA-positive vascular smooth muscle cells (VSMCs, while PEG control decidual vessels were remodelled by cytokeratin-positive trophoblasts. LIF blockade did not alter F4/80-positive decidual macrophage numbers between treatment groups, but resulted in down-regulation of decidual transcript levels of monocyte chemoattractant protein-1 (MCP-1 and interleukin-10 (IL-10, which are important immune cell activation factors that promote spiral artery remodeling during pregnancy. Our data suggest that LIF plays an important role in trophoblast invasion in vivo and may facilitate trophoblast-decidual-immune cell cross talk to enable adequate spiral artery remodeling.

  5. THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

    Institute of Scientific and Technical Information of China (English)

    杨成; 王胜发; 梁桃; 王巨; 王凯; 王柏春

    2001-01-01

    Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression.Methods. Thirty rats were divided into hypoxia group(10%O2, 8h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)technique was used to detect nucleosomal DNA fragmentation of apoptotic cells.In situ hybridization and RT-PCR were used to detect the expression level of bcl-2 and bax.``Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bcl-2 increased whereas bax decreased significantly in the hypoxic group.``Conclusion. The alternation in bcl-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

  6. THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

    Institute of Scientific and Technical Information of China (English)

    王巨; 王凯; 王柏春; 杨成; 王胜发; 梁桃

    2001-01-01

    Objective. To investigate the roles of apeptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group(10%O2, 8h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and fight ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediateddUTP nick-end labeling(TUNEL)technique was used to detect nucleosomal DNA fragmentation of apeptotic cells.In situ hybridization and RT-PCR were used to detect the expression level of bel-2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apeptotic cells can be found in lung with hypoxia or without hypexia. Compared with control group, apeptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bel-2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bel-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of p~monary hypertension secondary to hypoxia.

  7. Effects of weight loss and insulin reduction on arterial stiffness in the SAVE trial

    Directory of Open Access Journals (Sweden)

    Hughes Timothy M

    2012-09-01

    Full Text Available Abstract Background Chronic arterial stiffness contributes to the negative health effects of obesity and insulin resistance, which include hypertension, stroke, and increased cardiovascular and all-cause mortality. Weight loss and improved insulin sensitivity are individually associated with improved central arterial stiffness; however, their combined effects on arterial stiffness are poorly understood. The purpose of this study was to determine how insulin levels modify the improvements in arterial stiffness seen with weight loss in overweight and obese young adults. Methods To assess the effects of weight loss and decreased fasting insulin on vascular stiffness, we studied 339 participants in the Slow the Adverse Effects of Vascular Aging (SAVE trial. At study entry, the participants were aged 20–45, normotensive, non-diabetic, and had a body-mass index of 25–39.9 kg/m2. Measures of pulse wave velocity (PWV in the central (carotid-femoral (cfPWV, peripheral (femoral-ankle (faPWV, and mixed (brachial-ankle (baPWV vascular beds were collected at baseline and 6 months. The effects of 6-month change in weight and insulin on measures of PWV were estimated using multivariate regression. Results After adjustment for baseline risk factors and change in systolic blood pressure, 6-month weight loss and 6-month change in fasting insulin independently predicted improvement in baPWV but not faPWV or cfPWV. There was a significant interaction between 6-month weight change and change in fasting insulin when predicting changes in baPWV (p baPWV. Conclusions Young adults with excess weight who both lower their insulin levels and lose weight see the greatest improvement in vascular stiffness. This improvement in vascular stiffness with weight loss and insulin declines may occur throughout the vasculature and may not be limited to individual vascular beds. Trial registration NCT00366990

  8. Signaling of the p21-activated kinase (PAK1) coordinates insulin-stimulated actin remodeling and glucose uptake in skeletal muscle cells.

    Science.gov (United States)

    Tunduguru, Ragadeepthi; Chiu, Tim T; Ramalingam, Latha; Elmendorf, Jeffrey S; Klip, Amira; Thurmond, Debbie C

    2014-11-15

    Skeletal muscle accounts for ∼ 80% of postprandial glucose clearance, and skeletal muscle glucose clearance is crucial for maintaining insulin sensitivity and euglycemia. Insulin-stimulated glucose clearance/uptake entails recruitment of glucose transporter 4 (GLUT4) to the plasma membrane (PM) in a process that requires cortical F-actin remodeling; this process is dysregulated in Type 2 Diabetes. Recent studies have implicated PAK1 as a required element in GLUT4 recruitment in mouse skeletal muscle in vivo, although its underlying mechanism of action and requirement in glucose uptake remains undetermined. Toward this, we have employed the PAK1 inhibitor, IPA3, in studies using L6-GLUT4-myc muscle cells. IPA3 fully ablated insulin-stimulated GLUT4 translocation to the PM, corroborating the observation of ablated insulin-stimulated GLUT4 accumulation in the PM of skeletal muscle from PAK1(-/-) knockout mice. IPA3-treatment also abolished insulin-stimulated glucose uptake into skeletal myotubes. Mechanistically, live-cell imaging of myoblasts expressing the F-actin biosensor LifeAct-GFP treated with IPA3 showed blunting of the normal insulin-induced cortical actin remodeling. This blunting was underpinned by a loss of normal insulin-stimulated cofilin dephosphorylation in IPA3-treated myoblasts. These findings expand upon the existing model of actin remodeling in glucose uptake, by placing insulin-stimulated PAK1 signaling as a required upstream step to facilitate actin remodeling and subsequent cofilin dephosphorylation. Active, dephosphorylated cofilin then provides the G-actin substrate for continued F-actin remodeling to facilitate GLUT4 vesicle translocation for glucose uptake into the skeletal muscle cell.

  9. Role of infarction artery status in left ventricular remodeling after acute myocardial infarction.

    Science.gov (United States)

    Sanchis, J; Insa, L; Bodí, V; Egea, S; Monmeneu, J V; Chorro, F J; Llácer, A; López Merino, V

    1997-04-18

    The aim of this study was to evaluate the relation between the infarction artery status and left ventricular volumes, independently of regional ventricular dysfunction, at 4-6 weeks after a first myocardial infarction. The study group consisted of 100 patients, of whom 80 received thrombolytic treatment. Coronary and contrast left ventricular angiograms were performed at 36+/-5 days postinfarction. Left ventricular end-diastolic and end-systolic volumes were measured. The centerline chord motion method was used to calculate the extent of wall motion abnormality (percentage of chords with hypokinetic motion) and its severity (maximum units of S.D. below the normal wall motion reference). Minimum lumen diameter, patency and collateral flow in the infarction artery were also analyzed. Eight patients (group I) showed occlusion with poor collateral flow in the infarction artery, 22 patients (group II) occlusion with good collateral flow, 38 patients (group III) severe residual stenosis (minimum lumen diameter 1 mm). Patients from group I presented greater wall motion abnormality in terms of both extent (P=0.005) and severity (P=0.007), and greater end-diastolic (P=0.07) and end-systolic (P=0.0008) volumes; there were no differences among groups II, III and IV. By stepwise multivariate regression analysis, the extent of wall motion abnormality was the main determinant of end-diastolic (P=0.0001) and end-systolic (P=0.0001) volumes; occlusion with poor collateral flow was also a significant independent factor for end-systolic volume (P=0.03). Total occlusion (including both with and without collaterals) and the minimum lumen diameter did not correlate with end-diastolic and end-systolic volumes. We concluded that (A) the extent of regional dysfunction is the primary determinant of left ventricular volumes at 4-6 weeks postinfarction. (B) The status of the infarction artery is a weak predictor of end-diastolic volume, which is the best descriptor of ventricular remodeling

  10. Carotid thin fluttering bands: A new element of arterial wall remodelling? An ultrasound study.

    Science.gov (United States)

    Costanzo, Luca; Sole, Andrea; Tamburino, Corrado; Di Pino, Luigi

    2015-10-01

    Carotid artery ultrasound is a non-invasive and reproducible technique used for early atherosclerotic assessment. Intimal flap has been described in the presence of dissection or mobile plaque rupture, however presence of carotid thin fluttering bands (TFBs) have not been described yet. To investigate frequency, characteristics and impact of TFBs in carotid lumen of patients who underwent carotid ultrasound scan (CUS). 3341 patients were admitted from January 2009 to January 2014. Patients with history of cerebral ischemia (CI) were excluded. In the cases in which TFBs were observed, a 3-months clinical and CUS follow-up (FU) was performed. TFBs were found in 71 patients (2.1%). The mean age was 63.41 ± 11.20 years (range 42-89). All patients showed a mean increase in intima-media thickness. We identified two subgroups: in 22 patients the TFB was related to a carotid plaque while in 49 no carotid plaque was found. TFB mostly originated in the carotid bulb (88.7%) and was similarly located in carotid arteries (49.3% left-side and 50.7% right-side). CUS and clinical FU were available for all patients (mean duration 25.34 months, median 19). CI occurred in none of the patients. TFB disappeared in 13 patients (18.3%) with no sign or symptoms of CI. In 3 of 49 patients without carotid plaque (6.1%), progressive thickening beneath TFB was observed. TFB is a rare finding. Longer FU is needed to evaluate its prognosis. To date, the pathophysiology is unknown, however it could be related to vascular remodeling. PMID:26179862

  11. Early teatment with hepatocyte growth factor improves pulmonary artery and right ventricular remodeling in rats with pulmonary artery hypertension by modulating cytokines expression

    Institute of Scientific and Technical Information of China (English)

    王晓林

    2014-01-01

    Objective To investigate the effect of early treatment with hepatocyte growth factor(HGF)on the cytokine expression and pulmonary artery,right ventricular(RV)remodeling in the rat model of pulmonary artery hypertension(PAH).Methods The rat model of PAH was produced by injecting monocrotaline,and the model rats were randomly divided into empty adenovirus transfection group(MCT group,n=10)and HGF gene transfection group(HGF group,n=10).Another group of rats served as the Sham operation group(Sham group n=10).After 4 weeks of HGF gene transfection,the histological sections of the lungs and right ventricular(RV)

  12. Structural-functional State and feature remodeling of left ventricle in patients with coronary artery disease after revascularization

    OpenAIRE

    ALYAVI ANIS LUTFULLAEVICH; KAMILOVA UMIDA KABIROVNA; TULAGANOVA DILDORA KARIMOVNA; RADJABOVA DIYORA ISKANDAROVNA; SHODIEV JASUR DAVLATOVICH

    2016-01-01

    The article estimated the dynamics of systolic and diastolic function in patients with acute myocardial infarction after myocardial revascularization. The study involved 42 patients with acute myocardial infarction with ST segment elevation up to 6 hours of onset. Primary stenting of the infarct-related artery in patients with acute myocardial infarction with ST segment elevation allows most early as possible to prevent the development of pathological remodeling of the left ventricle compared...

  13. Trophoblast- and Vascular Smooth Muscle Cell-Derived MMP-12 Mediates Elastolysis during Uterine Spiral Artery Remodeling

    OpenAIRE

    Harris, Lynda K.; Smith, Samantha D.; Rosemary J Keogh; Jones, Rebecca L; Philip N Baker; Knöfler, Martin; Cartwright, Judith E.; Whitley, Guy St J; John D Aplin

    2010-01-01

    During the first trimester of pregnancy, the uterine spiral arteries are remodeled, creating heavily dilated conduits that lack maternal vasomotor control but allow the placenta to meet an increasing requirement for nutrients and oxygen. To effect permanent vasodilatation, the internal elastic lamina and medial elastin fibers must be degraded. In this study, we sought to identify the elastolytic proteases involved in this process. Primary first-trimester cytotrophoblasts (CTBs) derived from t...

  14. Differential Progressive Remodeling of Coronary and Cerebral Arteries and Arterioles in an Aortic Coarctation Model of Hypertension

    Directory of Open Access Journals (Sweden)

    Heather N. Hayenga

    2012-11-01

    Full Text Available OBJECTIVES: Effects of hypertension on arteries and arterioles often manifest first as a thickened wall, with associated changes in passive material properties (e.g., stiffness or function (e.g., cellular phenotype, synthesis and removal rates, and vasomotor responsiveness. Less is known, however, regarding the relative evolution of such changes in vessels from different vascular beds.METHODS: We used an aortic coarctation model of hypertension in the mini-pig to elucidate spatiotemporal changes in geometry and wall composition (including layer-specific thicknesses as well as presence of collagen, elastin, smooth muscle, endothelial, macrophage, and hematopoietic cells in three different arterial beds, specifically aortic, cerebral, and coronary, and vasodilator function in two different arteriolar beds, the cerebral and coronary.RESULTS: Marked geometric and structural changes occurred in the thoracic aorta and left anterior descending coronary artery within 2 weeks of the establishment of hypertension and continued to increase over the 8-week study period. In contrast, no significant changes were observed in the middle cerebral arteries from the same animals. Consistent with these differential findings at the arterial level, we also found a diminished nitric oxide-mediated dilation to adenosine at 8 weeks of hypertension in coronary arterioles, but not cerebral arterioles.CONCLUSION: These findings, coupled with the observation that temporal changes in wall constituents and the presence of macrophages differed significantly between the thoracic aorta and coronary arteries, confirm a strong differential progressive remodeling within different vascular beds. Taken together, these results suggest a spatiotemporal progression of vascular remodeling, beginning first in large elastic arteries and delayed in distal vessels.

  15. Pregnancy prevents hypertensive remodeling and decreases myogenic reactivity in posterior cerebral arteries from Dahl salt-sensitive rats : a role in eclampsia?

    NARCIS (Netherlands)

    Aukes, Annet M.; Vitullo, Lisa; Zeeman, Gerda G.; Cipolla, Marilyn J.

    2007-01-01

    Previous studies have demonstrated that pregnancy prevents protective hypertension-induced remodeling of cerebral arteries using nitric oxide synthase (NOS) inhibition to raise mean arterial pressure (MAP). In the present study, we investigated whether this effect of pregnancy was specific to NOS in

  16. Maternal carotid remodeling and increased carotid arterial stiffness in normal late-gestational pregnancy as assessed by radio-frequency ultrasound technique

    OpenAIRE

    Yuan, Li-Jun; Xue, Dan; DUAN, YUN-YOU; Cao, Tie-Sheng; Zhou, Ning

    2013-01-01

    Background The adaption of elastic arteries to transient increase in hemodynamic load in normal pregnancy (NP) remains controversial. The purpose of this study was to investigate the NP carotid remodeling and regional arterial stiffness before and after parturition. Methods Fifty-one NP women and 30 age-matched non-pregnant women were included. All women underwent right common carotid artery (RCCA) measurements with MylabTwice ultrasound instrument (Esaote, Italy). Carotid intima-medial thick...

  17. Postlipolytic insulin-dependent remodeling of micro lipid droplets in adipocytes

    OpenAIRE

    Ariotti, Nicholas; Murphy, Samantha; Hamilton, Nicholas A; Wu, Lizhen; Green, Kathryn; Nicole L Schieber; Li, Peng; Martin, Sally; Parton, Robert G.

    2012-01-01

    Despite the lipolysis–lipogenesis cycle being a fundamental process in adipocyte biology, very little is known about the morphological changes that occur during this process. The remodeling of lipid droplets to form micro lipid droplets (mLDs) is a striking feature of lipolysis in adipocytes, but once lipolysis ceases, the cell must regain its basal morphology. We characterized mLD formation in cultured adipocytes, and in primary adipocytes isolated from mouse epididymal fat pads, in response...

  18. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

    Directory of Open Access Journals (Sweden)

    Rosa L.E. Loon

    2015-08-01

    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  19. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    Science.gov (United States)

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity. PMID:27207538

  20. Role of TGF beta signaling in Remodeling of Non-Coronary Artery Aneurysms in Kawasaki disease /

    OpenAIRE

    Lee, Aaron Ming

    2014-01-01

    Coronary artery aneurysms remain a life-threatening complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries (1). Potentially life-threatening coronary artery aneurysms (CAA) develop in 25% of untreated children and 5% of children treated with high dose intravenous immunoglobulin during the acute phase of the self-limited vasculitis (2). Non-coronary artery aneurysms (NCAA) in extra-parenchymal, muscular arteries occur in a minorit...

  1. Mechanical properties of mesenteric arteries in diabetic rats : consequences of outward remodeling

    NARCIS (Netherlands)

    Crijns, F R; Wolffenbuttel, B H; De Mey, J G; Struijker Boudier, H A

    1999-01-01

    Diabetes induces hemodynamic and biochemical changes that can influence mechanical properties of arteries. Structure and mechanics of mesenteric small arteries were investigated in rats with streptozotocin-induced diabetes (duration 7-9 wk). The external diameter of mesenteric artery branches was me

  2. Insulin

    Science.gov (United States)

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  3. Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

    Directory of Open Access Journals (Sweden)

    Feugier Patrick

    2009-12-01

    Full Text Available Abstract Background Vascular smooth muscular cells (VSMC express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma. Methods We investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma. Results Zucker obese (ZO and diabetic (ZDF rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM. Conclusion Lipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.

  4. Progressive vascular remodelling, endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Quek, K J; Boyd, R; Ameer, O Z; Zangerl, B; Butlin, M; Murphy, T V; Avolio, A P; Phillips, J K

    2016-06-01

    Chronic kidney disease (CKD) and hypertension are co-morbid conditions both associated with altered resistance artery structure, biomechanics and function. We examined these characteristics in mesenteric artery together with renal function and systolic blood pressure (SBP) changes in the Lewis polycystic kidney (LPK) rat model of CKD. Animals were studied at early (6-weeks), intermediate (12-weeks), and late (18-weeks) time-points (n=21), relative to age-matched Lewis controls (n=29). At 12 and 18-weeks, LPK arteries exhibited eutrophic and hypertrophic inward remodelling characterised by thickened medial smooth muscle, decreased lumen diameter, and unchanged or increased media cross-sectional area, respectively. At these later time points, endothelium-dependent vasorelaxation was also compromised, associated with impaired endothelium-dependent hyperpolarisation and reduced nitric oxide synthase activity. Stiffness, elastic-modulus/stress slopes and collagen/elastin ratios were increased in 6 and 18-week-old-LPK, in contrast to greater arterial compliance at 12weeks. Multiple linear regression analysis highlighted SBP as the main predictor of wall-lumen ratio (r=0.536, Pdisease. PMID:26771067

  5. Large Artery Remodeling and Dynamics following Simulated Microgravity by Prolonged Head-Down Tilt Bed Rest in Humans

    Directory of Open Access Journals (Sweden)

    Carlo Palombo

    2015-01-01

    Full Text Available The effects of simulated microgravity on the static and dynamic properties of large arteries are still mostly unknown. The present study evaluated, using an integrated vascular approach, changes in structure and function of the common carotid and femoral arteries (CCA and CFA after prolonged head-down tilt bed rest (HDTBR. Ten healthy men were enrolled in a 5-week HDTBR study endorsed by the Italian Space Agency (ASI. Arterial geometry, flow, stiffness, and shear rate were evaluated by ultrasound. Local carotid pulse pressure and wave reflection were studied by applanation tonometry. After five weeks of HDTBR, CFA showed a decrease in lumen diameter without significant changes in wall thickness (IMT, resulting in an inward remodeling. Local carotid pulse pressure decreased and carotid-to-brachial pressure amplification increased. The ratio of systolic-to-diastolic volumetric flow in CFA decreased, whereas in CCA it tended to increase. Indices of arterial stiffness and shear rate did not change during HDTBR, either in CCA or CFA. In summary, prolonged HDTBR has a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused.

  6. Obese children and adolescents have elevated nighttime blood pressure independent of insulin resistance and arterial stiffness

    DEFF Research Database (Denmark)

    Hvidt, Kristian N; Olsen, Michael H; Holm, Jens-Christian;

    2014-01-01

    BACKGROUND: Insulin resistance has been related to elevated blood pressure (BP) in obese children and may adversely affect the vasculature by arterial stiffening. The objective was to investigate whether daytime and nighttime BP were elevated and related to insulin resistance and arterial stiffness...... in obese children and adolescents. METHODS: Ninety-two obese patients aged 10-18 years were compared with 49 healthy control individuals. Insulin resistance was measured as the homeostatic assessment model (HOMA), and arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). RESULTS......: Mean ± SD daytime systolic BP (SBP) (obese: 125±8.3mm Hg; control: 121±10.1mm Hg; P = 0.03) and nighttime SBP (obese: 108±10.7mm Hg; control: 102±8.2mm Hg; P = 0.0001) were higher in the obese group when compared with the control group. No difference was found in daytime diastolic BP (DBP), whereas...

  7. Role of TGF-β signaling in remodeling of noncoronary artery aneurysms in kawasaki disease

    OpenAIRE

    Lee, AM; Shimizu, C.; Oharaseki, T; K. Takahashi; Daniels, LB; Kahn, A.; Adamson, R.; Dembitsky, W; Gordon, JB; Burns, JC

    2015-01-01

    © 2015 Society for Pediatric Pathology. Coronary artery aneurysms (CAA) remain an important complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries. Potentially life-threatening CAA develop in 25% of untreated children and 5% of children treated with highdose intravenous immunoglobulin during the acute phase of the self-limited vasculitis. Noncoronary artery aneurysms (NCAA) in extraparenchymal, muscular arteries occur in aminorit...

  8. Arterial stiffness in insulin resistance: The role of nitric oxide and angiotensin II receptors

    Directory of Open Access Journals (Sweden)

    Divina G Brillante

    2008-12-01

    Full Text Available Divina G Brillante1, Anthony J O’Sullivan1, Laurence G Howes21St. George Clinical School, University of New South Wales, Kogarah, NSW, Australia; 2Department of Pharmacology and Therapeutics and Department of Cardiology, Griffith and Bond University, Gold Coast Hospital, Southport, QLD, AustraliaAbstract: The insulin resistance syndrome (INSR is associated with increased cardiovascular risk, and affects up to 25% of the Australian population aged >20 years. Increased arterial stiffness has been proposed as a common pathway by which INSR leads to increased cardiovascular risk. We have reviewed the role of nitric oxide (NO and angiotensin II receptors in the modulation of arterial stiffness in the setting of insulin resistance. There is emerging evidence that early stages of INSR may be characterized by increased basal nitric oxide activity and increased activity of non-NO vasodilators such as endothelial derived hyperpolarization factor (EDHF which is manifest by reduced arterial stiffness. Depletion of NO or ineffectiveness of NO mediated vasodilator mechanisms associated with the progression of INSR to type 2 diabetes may result in increased arterial stiffness, which predicts the development of cardiovascular disease. Thus in the early stages of INSR, increased NO and EDHF activity may represent compensatory mechanisms to early vascular damage. The renin-angiotensin system is activated in diseased vascular beds, with up regulation of the two known angiotensin II receptors: the angiotensin II type 1 receptor (AT1R and the angiotensin II type 2 receptor (AT2R. Increased AT1R mediated activity in the vasculature is central to the development of increased arterial stiffness and is enhanced in INSR states. AT2R activity is increased in early in INSR and may contribute to the apparent increase in basal NO activity. AT1R blockade may therefore be valuable treatment for early INSR as antagonism of AT1 receptors would allow angiotensin II to act

  9. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  10. Need for insulin to control gestational diabetes is reflected in the ambulatory arterial stiffness index

    Directory of Open Access Journals (Sweden)

    Kärkkäinen Henna

    2013-01-01

    Full Text Available Abstract Background The aim was to evaluate the metabolic profile in conjunction with vascular function using the ambulatory arterial stiffness index (AASI in women with uncomplicated pregnancies and in women with gestational diabetes mellitus (GDM. Methods Plasma glucose, lipids, HOMA –IR (homeostasis model assessment of insulin resistance and AASI, as obtained from 24-hour ambulatory blood pressure monitoring in third trimester pregnancy and at three months postpartum, were measured in three groups of women: controls (N = 32, women with GDM on diet (N = 42 and women with GDM requiring insulin treatment (N = 10. Results Women with GDM had poorer glycemic control and higher HOMA-IR during and after pregnancy and their total and LDL (low density lipoprotein cholesterol levels were significantly higher after pregnancy than in the controls. After delivery, there was an improvement in AASI from 0.26 ± 0.10 to 0.17 ± 0.09 (P = 0.002 in women with GDM on diet, but not in women with GDM receiving insulin whose AASI tended to worsen after delivery from 0.30 ± 0.23 to 0.33 ± 0.09 (NS, then being significantly higher than in the other groups (P = 0.001-0.047. Conclusions Women with GDM had more unfavorable lipid profile and higher blood glucose values at three months after delivery, the metabolic profile being worst in women requiring insulin. Interestingly, the metabolic disturbances at three months postpartum were accompanied by a tendency towards arterial stiffness to increase in women requiring insulin.

  11. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

    DEFF Research Database (Denmark)

    Muscelli, Elza; Kozàkovà, Michaela; Flyvbjerg, Allan;

    2009-01-01

    secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. METHODS: In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid...... mathematical modeling. RESULTS: CCA diameter (5.55 +/- 0.46 vs. 5.21+/- 0.51 mm, P < 0.001), CCA IMT (608 +/- 78 vs. 576 +/- 74 microm, P < 0.01) and systolic blood pressure (BP) (117 +/- 12 vs. 113 +/- 11 mm Hg, P < 0.05) were higher in menopausal women, whereas CCA IMT/diameter ratio and IMT in other carotid...

  12. EFFECT OF INFLIXIMAB ON PARAMETERS OF REMODELING OF ARTERIAL BLOODSTREAM, RANKL AND OSTEOPROTEGERIN LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Larisa Aleksandrovna Knyazeva

    2013-01-01

    Full Text Available Objective. To study the effect of infliximab (INF on serum levels of RANKL and osteoprotegerin (OPG, as well as on structural and functional properties of the vascular wall in patients with rheumatoid arthritis (RA.Material and Methods. A total of 79 RA patients who corresponded to the classification criteria ACR (1987 or ACR/EULAR (2010 and were seronegative for IgM rheumatoid factor (RF were examined. The mean age of patients was 43.6±8.5 years. The serum levels of OPG and RANKL were determined by ELISA (Biomedica, Austria; the common carotid arteries (CCAs were visualized using an Acuson X/10 ultrasonic complex equipped with a 7 MHz linear sensor in the β-mode prior to therapy and after 12-month therapy with INF.Results and Discussion. An increased OPG level was observed mostly in patients with RA duration up to 1 year; an increase in RANKL level was pronounced stronger in patients with PA duration over 2 years. The disturbance of structural and functional properties of the arterial bloodstream was revealed, manifesting itself as an increase in the intimamedia complex thickness, diameter and rigidity index of CCA that were stronger pronounced in patients with late onset RA. A correlation analysis showed the presence of reliable relationship between the RANKL and OPG levels and CCA remodeling parameters. INF therapy showed high clinical effectiveness and correction effect on the RANKL/OPG system. In addition, it was accompanied by a reduction of signs of CCA remodeling, which was stronger pronounced in patients with early RA.Conclusion. The results prove the reasonability of using INF at early stages of RA in order to optimize the therapy and achieve more efficient control of cardiovascular complications.

  13. Multi-Layer Mechanical Model of Glagov Remodeling in Coronary Arteries: Differences between In-Vivo and Ex-Vivo Measurements.

    Directory of Open Access Journals (Sweden)

    Pak-Wing Fok

    Full Text Available When blood vessels undergo remodeling because of the buildup of atherosclerotic plaque, it is thought that they first undergo compensatory or outward remodeling, followed by inward remodeling: the lumen area stays roughly constant or increases slightly and then decreases rapidly. The second phase of remodeling is supposed to start after the plaque burden exceeds about 40%. These changes in the vessel were first observed by S. Glagov who examined cross-sections of coronary arteries at different stages of the disease. In this paper, we use a mathematical model based on growth and elasticity theory to verify the main aspects of Glagov's result. However, both our model and curve-fitting to the data suggest that the critical stenosis is around 20% rather than 40%. Our model and data from the PROSPECT trial also show that Glagov remodeling is qualitatively different depending on whether measurements are taken ex-vivo or in-vivo. Our results suggest that the first outward phase of "Glagov remodeling" is largely absent for in-vivo measurements: that is, the lumen area always decreases as plaque builds up. We advocate that care must be taken when infering how in-vivo vessels remodel from ex-vivo data.

  14. Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.

    Directory of Open Access Journals (Sweden)

    Irina Strazhesko

    Full Text Available Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL, and arterial stiffness (core feature of arterial aging, as measured by carotid-femoral pulse wave velocity (c-f PWV.The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001 and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001 and independently negatively associated with LTL (p = 0.0378. HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001 and age (p = 0.0001. In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk.

  15. Permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure.

    Science.gov (United States)

    Muthuramu, Ilayaraja; Lox, Marleen; Jacobs, Frank; De Geest, Bart

    2014-12-02

    Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure. Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling. Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.

  16. Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Sharifah Intan Qhadijah Syed Ikmal

    2013-01-01

    Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

  17. Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Mediated Redox Signaling and Vascular Remodeling by 16α-Hydroxyestrone in Human Pulmonary Artery Cells: Implications in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Hood, Katie Y; Montezano, Augusto C; Harvey, Adam P; Nilsen, Margaret; MacLean, Margaret R; Touyz, Rhian M

    2016-09-01

    Estrogen and oxidative stress have been implicated in pulmonary arterial hypertension (PAH). Mechanisms linking these systems are elusive. We hypothesized that estrogen metabolite, 16α-hydroxyestrone (16αOHE1), stimulates nicotinamide adenine dinucleotide phosphate oxidase (Nox)-induced reactive oxygen species (ROS) generation and proliferative responses in human pulmonary artery smooth muscle cells (hPASMCs) and that in PAH aberrant growth signaling promotes vascular remodeling. The pathophysiological significance of estrogen-Nox-dependent processes was studied in female Nox1(-/-) and Nox4(-/-) mice with PAH. PASMCs from control subjects (control hPASMCs) and PAH patients (PAH-hPASMCs) were exposed to estrogen and 16αOHE1 in the presence/absence of inhibitors of Nox, cytochrome P450 1B1, and estrogen receptors. Estrogen, through estrogen receptor-α, increased Nox-derived ROS and redox-sensitive growth in hPASMCs, with greater effects in PAH-hPASMCs versus control hPASMCs. Estrogen effects were inhibited by cytochrome P450 1B1 blockade. 16αOHE1 stimulated transient ROS production in hPASMCs, with sustained responses in PAH-hPASMCs. Basal expression of Nox1/Nox4 was potentiated in PAH-hPASMCs. In hPASMCs, 16αOHE1 increased Nox1 expression, stimulated irreversible oxidation of protein tyrosine phosphatases, decreased nuclear factor erythroid-related factor 2 activity and expression of nuclear factor erythroid-related factor 2-regulated antioxidant genes, and promoted proliferation. This was further amplified in PAH-hPASMCs. Nox1(-/-) but not Nox4(-/-) mice were protected against PAH and vascular remodeling. Our findings demonstrate that in PAH-hPASMCs, 16αOHE1 stimulates redox-sensitive cell growth primarily through Nox1. Supporting this, in vivo studies exhibited protection against pulmonary hypertension and remodeling in Nox1(-/-) mice. This study provides new insights through Nox1/ROS and nuclear factor erythroid-related factor 2 whereby 16αOHE1 influences

  18. Diet-induced hyperhomocysteinemia exacerbates vascular reverse remodeling of balloon-injured arteries in rat

    Institute of Scientific and Technical Information of China (English)

    GUO Yan-hong; CHEN Feng-ying; WANG Gui-song; CHEN Li; GAO Wei

    2008-01-01

    Background While hyperhomocysteinemia is associated with an increased risk of cardiovascular diseases,the effect of hyperhomocysteinemia on the vascular adventitia and vessel remodeling has not been clearly demonstrated.We investigated the effect of the hyperhomocysteinemia on adventitial hyperplasia and vascular remodeling following balloon injury in rats and the underlying mechanisms.Methods Rats were fed with diet containing methionine for 4 weeks to increase plasma homocysteine before balloon injury.Vascular geometrical changes were assessed at different time points following balloon injury.The collagen deposition was determined by picrosirius red staining and immunohistochemical staining.Results When compared with normal diet group,moderate hyperhomocysteinemia in methionine diet group significantly exacerbated adventitial hyperplasia at clay 7 and collagen deposition mainly in the adventitia at day 28 following balloon injury.The increased plasma homocysteine level significantly increased collagen deposition in the adventitia.There was a negative correlation (r=0.698;P <0.01) between the luminal area and the collagen content in the adventitia on day 28 following balloon injury.In cultured adventitial fibroblasts isolated from rat aorta,100 μmol/L L-homocysteine (L-Hcy) significantly down-regulated matrix metalloproteinase-2 activity by 43% as determined by in vitro gelatin zymography (P <0.05) and up-regulated the expression of collagen type 1 by 187% (P <0.05) assessed by Western blotting.Conclusions Hyperhomocysteinemia exacerbated vascular constrictive remodeling by accelerated neointima formation and collagen accumulation in the adventitia.Increased collagen deposition may be the underlying mechanism.

  19. Prognosis parameters and polarimetric properties of erythrocytes of the patients suffering from arterial hypertension and coronary heart disease at various patterns of left ventricular remodeling

    Science.gov (United States)

    Ivaschuk, Oleg I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Ya.

    2012-01-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  20. Angioplasty and stenting for severe vertebral artery oriifce stenosis:effects on cerebellar function remodeling veriifed by blood oxygen level-dependent functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Bo Liu; Zhiwei Li; Peng Xie

    2014-01-01

    Vertebral artery oriifce stenting may improve blood supply of the posterior circulation of the brain to regions such as the cerebellum and brainstem. However, previous studies have mainly focused on recovery of cerebral blood lfow and perfusion in the posterior circulation after inter-ventional therapy. This study examined the effects of functional recovery of local brain tissue on cerebellar function remodeling using blood oxygen level-dependent functional magnetic reso-nance imaging before and after interventional therapy. A total of 40 Chinese patients with severe unilateral vertebral artery oriifce stenosis were enrolled in this study. Patients were equally and randomly assigned to intervention and control groups. The control group received drug treat-ment only. The intervention group received vertebral artery oriifce angioplasty and stenting+identical drug treatment to the control group. At 13 days after treatment, the Dizziness Handicap Inventory score was compared between the intervention and control groups. Cerebellar function remodeling was observed between the two groups using blood oxygen level-dependent function-al magnetic resonance imaging. The improvement in dizziness handicap and cerebellar function was more obvious in the intervention group than in the control group. Interventional therapy for severe vertebral artery oriifce stenosis may effectively promote cerebellar function remodeling and exert neuroprotective effects.

  1. THE ROLE OF GENETIC FACTORS IN THE MECHANISM OF CORONARY ARTERY REMODELING AFTER IMPLANTATION OF STENTS

    Directory of Open Access Journals (Sweden)

    S. I. Vintizenko

    2015-01-01

    Full Text Available In the last 10 years the World has increased significantly the frequency of joint replacement in patients with coronary artery disease. Coronary angioplasty with stenting significantly improve the capacity and effectiveness of the treatment of coronary artery disease. However, an important factor limiting the effectiveness of endovascular treatment of restenosis remains the stented area.The article presents an overview of the most studied gene polymorphisms of hemostasis, inflammation system, the renin-angiotensin system, endothelial nitric oxide synthase, which can play a key role in the development of in-stent restenosis. Research in this area are significant and may help in understanding the mechanisms and risk stratification of restenosis after angioplasty.

  2. Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep

    OpenAIRE

    Dodson, R. Blair; Morgan, Matthew R.; Galambos, Csaba; Hunter, Kendall S.; Abman, Steven H.

    2014-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characteriz...

  3. Arterialization and anomalous vein wall remodeling in varicose veins is associated with upregulated FoxC2-Dll4 pathway.

    Science.gov (United States)

    Surendran, Sumi; S Ramegowda, Kalpana; Suresh, Aarcha; Binil Raj, S S; Lakkappa, Ravi Kumar B; Kamalapurkar, Giridhar; Radhakrishnan, N; C Kartha, Chandrasekharan

    2016-04-01

    Varicose veins of lower extremities are a heritable common disorder. Mechanisms underlying its pathogenesis are still vague. Structural failures such as valve weakness and wall dilatation in saphenous vein result in venous retrograde flow in lower extremities of body. Reflux of blood leads to distal high venous pressure resulting in distended veins. In an earlier study, we observed a positive association between c.-512C>T FoxC2 gene polymorphism and upregulated FoxC2 expression in varicose vein specimens. FoxC2 overexpression in vitro in venous endothelial cells resulted in the elevated mRNA expression of arterial endothelial markers such as Delta-like ligand 4 (Dll4) and Hairy/enhancer-of-split related with YRPW motif protein 2 (Hey2). We hypothesized that an altered FoxC2-Dll4 signaling underlies saphenous vein wall remodeling in patients with varicose veins. Saphenous veins specimens were collected from 22 patients with varicose veins and 20 control subjects who underwent coronary artery bypass grafting. Tissues were processed for paraffin embedding and sections were immunostained for Dll4, Hey2, EphrinB2, α-SMA, Vimentin, and CD31 antigens and examined under microscope. These observations were confirmed by quantitative real-time PCR and western blot analysis. An examination of varicose vein tissue specimens by immunohistochemistry indicated an elevated expression of Notch pathway components, such as Dll4, Hey2, and EphrinB2, and smooth muscle markers, which was further confirmed by gene and protein expression analyses. We conclude that the molecular alterations in Dll4-Hey2 signaling are associated with smooth muscle cell hypertrophy and hyperplasia in varicose veins. Our observations substantiate a significant role for altered FoxC2-Dll4 signaling in structural alterations of saphenous veins in patients with varicose veins.

  4. Impact of insulin like growth factor-1 in development of coronary artery ectasia

    Directory of Open Access Journals (Sweden)

    Ibrahim Faruk Akturk

    2014-09-01

    Full Text Available Coronary artery ectasia (CAE is characterized by inappropriate dilatation of the coronary vasculature. The mechanisms of CAE are not well known. Insulin-like growth factor-1 (IGF-1 may make endothelial cells and smooth muscle cells more sensitive to the effects of growth hormone. In the present study, we hypothesized that IGF-1 may have an impact on the formation of ectasia and aneurysm in arterial system, and aimed to investigate the associations between the presence of CAE and serum IGF-1 levels in patients undergoing coronary angiography. The study included 2.980 subjects undergoing elective diagnostic coronary angiography. We selected 40 patients diagnosed with CAE as CAE group and 44 subjects with absolutely normal coronary arteries were assigned as normal control group. IGF-1 levels were measured in both groups of patients. Groups were similar in terms of age, sex and coronary artery disease risk factors. The serum IGF-1 levels were significantly higher in CAE patients with 109.64±54.64 ng/mL than in controls with 84.76±34.01 ng/mL (p=0.016. HDL levels were lower in ectasia group with 41.5±10.7 mg/dL than controls with 47.7±10.4 mg/dL (p=0.018. By means of logistic regression analysis, high IGF-1 and low HDL levels were found to be independent risk factors for the presence of CAE (p<0.02, p<0.016, respectively. The study revealed that there was a positive correlation between serum IGF-1 levels and presence of CAE, and high IGF-1 levels and low HDL levels were independent risk factors for the presence of CAE. Future studies are needed to confirm these results.

  5. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpa......In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings...... in the chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental...... bed tissue, showing interstitial and spiral artery invasion of the inner myometrium as well as the decidua. The cell density and depth of trophoblast invasion was equivalent to a human placental bed of 10-14 weeks. Intraluminal trophoblasts were not seen in any of the invaded vessels, allowing...

  6. JNKs, insulin resistance and inflammation: A possible link between NAFLD and coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino; Armando Caputi

    2011-01-01

    The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem. Therefore, the contribution of adipose tissue to metabolic homeostasis has become a focus of interest. In this review, we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease. We describe the common mechanisms (c-Jun amino-terminal kinases, endoplasmic reticulum stress, unfolded protein response, ceramide, low-grade chronic inflammation) by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall. Presenting the molecular mechanism of lipid activation of pro-inflammatory pathways, we attempt to find a link between nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular diseases. Describing the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of pro-inflammatory pathways, the key roles played by the proliferator-activated receptor and liver X receptor α, nuclear receptors-lipid sensors that link lipid metabolism and inflammation, should be emphasized. Further studies are warranted of anti-inflammatory drugs such as aspirin, anti-interleukin-6 receptors, immune-modulators (calcineurin inhibitors), substances enhancing the expression of heat shock proteins (which protect cells from endoplasmic reticulum stress-induced apoptosis), and anti- c-Jun amino-terminal kinases in well-designed trials to try to minimize the high impact of these illnesses, and the different expressions of the diseases, on the whole population.

  7. Understanding How Space Travel Affects Blood Vessels: Arterial Remodeling and Functional Adaptations Induced by Microgravity

    Science.gov (United States)

    Delp, Michael; Vasques, Marilyn; Aquilina, Rudy (Technical Monitor)

    2002-01-01

    Ever rise quickly from the couch to get something from the kitchen and suddenly feel dizzy? With a low heart rate and relaxed muscles, the cardiovascular system does not immediately provide the resistance necessary to keep enough blood going to your head. Gravity wins, at least for a short time, before your heart and blood vessels can respond to the sudden change in position and correct the situation. Actually, the human cardiovascular system is quite well adapted to the constant gravitational force of the Earth. When standing, vessels in the legs constrict to prevent blood from collecting in the lower extremities. In the space environment, the usual head-to-foot blood pressure and tissue fluid gradients that exist during the upright posture on Earth are removed. The subsequent shift in fluids from the lower to the upper portions of the body triggers adaptations within the cardiovascular system to accommodate the new pressure and fluid gradients. In animal models that simulate microgravity, the vessels in the head become more robust while those in the lower limbs become thin and lax. Similar changes may also occur in humans during spaceflight and while these adaptations are appropriate for a microgravity environment, they can cause problems when the astronauts return to Earth or perhaps another planet. Astronauts often develop orthostatic intolerance which means they become dizzy or faint when standing upright. This dizziness can persist for a number of days making routine activities difficult. In an effort to understand the physiological details of these cardiovascular adaptations, Dr. Michael Delp at Texas A&M University, uses the rat as a model for his studies. For the experiment flown on STS-107, he will test the hypothesis that blood vessels in the rats' hindlimbs become thinner, weaker, and constrict less in response to pressure changes and to chemical signals when exposed to microgravity. In addition, he will test the hypothesis that arteries in the brain

  8. Role of TGF-β1/Smads pathway in carotid artery remodeling in renovascular hypertensive rats and prevention by Enalapril and Amlodipine

    Institute of Scientific and Technical Information of China (English)

    Jian-Ling Chen; Qian-Hui Shang; Wei Hu; Chan Liu; Wan-Heng Mao; Hua-Qing Liu

    2012-01-01

    Objective To investigate the role of transforming growth factor-β1 (TGF-β1), Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat (RHR) models with "two-kidney and one-clip" were established, including model group (n = 6), sham-operated group (n = 6), Enalapril group (10 mg/kg per day, n = 6), Amlodipine group (5 mg/kg per day, n = 6) and combination group (Amlodipine 2.5 mg/kg per day + Enalapril 5mg/kg per day, n = 6). The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness (MT), MT and lumen diameter ratio (MT/LD), and the expression levels of media α-smooth muscle actin (α-actin), proliferating cell nuclear antigen (PCNA), TGF-β1, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group (P < 0.01). Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 (P < 0.05) and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 (P < 0.05), increased Smad7 expression (P < 0.05). Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group (P < 0.05), but not

  9. The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice

    OpenAIRE

    Yu, Ying; Cai, Zhaohua; CUI, MINGLI; Nie, Peng; Sun, Zhe; SUN, SHIQUN; CHU, SHICHUN; Wang, Xiaolei; Hu, Liuhua; Yi, Jing; Shen, Linghong; He, Ben

    2015-01-01

    Shear stress, particularly low and oscillatory shear stress, plays a critical pathophysiological role in vascular remodeling-related cardiovascular diseases. Growing evidence suggests that the orphan nuclear receptor Nur77 [also known as TR3 or nuclear receptor subfamily 4, group A, member 1 (NR4A1)] is expressed in diseased human vascular tissue and plays an important role in vascular physiology and pathology. In the present study, we used a mouse model of flow-dependent remodeling by partia...

  10. Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries.

    Science.gov (United States)

    Peng, Xue; Li, Hong-Xia; Shao, Hong-Jiang; Li, Guang-Wei; Sun, Jian; Xi, Yu-Hui; Li, Hong-Zhu; Wang, Xin-Yan; Wang, Li-Na; Bai, Shu-Zhi; Zhang, Wei-Hua; Zhang, Li; Yang, Guang-Dong; Wu, Ling-Yun; Wang, Rui; Xu, Chang-Qing

    2014-11-01

    Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an important role during hypoxia-induced vascular remodeling and pulmonary hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR) is expressed in rat PASMCs. However, little is known about the role of CaSR in phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying mechanisms. In this study, we investigated whether CaSR induces the proliferation of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of medial wall thickness to the external diameter (WT %), and cross-sectional total vessel wall area to the total area (WA %) of small pulmonary arteries were determined by hematoxylin and eosin (HE), masson trichrome and Weigert's staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9, the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p-ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small pulmonary arteries, including calponin, SMα-actin (SMAα), and osteopontin (OPN), were analyzed by immunohistochemistry and Western blotting, respectively. In addition, immunohistochemistry was applied to paraffin-embedded human tissues from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF). Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were gradually increased with the prolonged hypoxia. At the same time, the expressions of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased, while the expressions of SMAα and calponin were significantly reduced in lung tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR) enhanced but NPS2390 (an

  11. Experimental study of arterialized vein graft remodeling%静脉桥动脉化后桥血管重塑的实验研究

    Institute of Scientific and Technical Information of China (English)

    赵智伟; Abendroth DK; 葛建军; 林敏; 周正春; 王海涛; 孔祥; 刘永志; 邬松; 周经月

    2011-01-01

    Objective To investigate the effect of vein graft arterialization on vein graft remodeling.Methods Thirty SD rats were randomly divided into the AVG group and the CON group.We established vein graft arterialization model using inproved cuff technique in AVG group with the external jugular vein graft to the ipsilateral common carotid artery , but in CON group, only simulated surgical environment, cut and stitched the skin, separated artery and vein without the vein arterialization.Respectively, after 1 week, 2 weeks, 4 weeks vein grafts and the control veins were harvested, and intimal and medial hyperplasia were sdudied by morphological analysis.Results No animal died in two groups.There was only one case of vein occlusion in AVG group at 4 weeks, the patency rate was 93.3% .Intimal and medial of the AVG group were significantly thicker than those of the CON group (P <0.05 or P < 0.01) .Conclusion AVG advances the intimal and medial hyperplasia, and accelerates vein grafts remodeling.%目的 探讨静脉动脉化(AVG)对静脉桥血管结构重塑的影响.方法 将30只SD大鼠随机分为实验组和对照组.实验组采用改良cuff法构建颈AVG模型,对照组仅模拟手术环境,切开和缝合皮肤、分离动静脉,未进行AVG.分别于术后1、2、4周取出静脉桥及对照组颈静脉,进行形态学分析,研究桥血管内膜和中膜的增生变化.结果 2组模型均无动物死亡.4周时实验组1只闭塞,通畅率93.3%.实验组1、2、4周时内膜及中膜均较对照组增厚(P<0.05或<0.01).结论 AVG使静脉桥血管内膜及中膜增生,加快了静脉桥血管的结构重塑.

  12. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during...

  13. CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko

    2015-09-01

    Full Text Available Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT.Material and methods. Patients (n=175, all are males with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction and nitroglycerin (endothelium independent reaction in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05 and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05. The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

  14. CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko

    2013-01-01

    Full Text Available Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT.Material and methods. Patients (n=175, all are males with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction and nitroglycerin (endothelium independent reaction in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05 and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05. The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

  15. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Smidt, U M; Friisberg, B;

    1981-01-01

    Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (greater than 0.5 g/day) secondary to diabetic...... and 112/mumol/l (NS), proteinuria increased from 1.8 to 3.3 g/day (p less than 0.001) and arterial blood pressure rose from 132/88 to 153/101 mmHg (p less than 0.001). Glomerular filtration rate decreased linearly with time (slope = -0.75, r = 0.99, p less than 0.001) by a mean of 0.75 ml/min/month (range...

  16. The Relationship among Carotid Artery Remodeling, Cardiac Geometry, and Serum N-Terminal Pro-B-Type Natriuretic Peptide Level in Asymptomatic Asians: Sex-Differences and Longitudinal GEE Study.

    Directory of Open Access Journals (Sweden)

    Chen-Yen Chien

    Full Text Available Carotid artery remodeling is known to be associated with a variety of cardiovascular diseases. However, there is limited information regarding gender differences in carotid remodeling. We sought to investigate the associations among blood pressure (BP, carotid artery remodeling and cardiac geometries, and further explore gender differences.In a large cohort of asymptomatic adults undergoing routine health screening with repeated observations, we related measures of carotid artery diameter (CCAD to various BP components, cardiac geometries and blood N-terminal pro-brain natriuretic peptide (NT-proBNP level, both from baseline cross-sectional and longitudinal dataset using generalized estimating equations (GEE.A total of 2,914 person-visits (baseline: n=998, mean age: 47 ± 8.9 years, 34% female were studied (median: 6 ± 1.73 years follow up. We observed that CCAD was larger in men (p=300pg/mL; AUROC: 0.79, CCAD cut-off: 7.95mm, all p<0.05, which remained significant in multi-variate and longitudinal models. There was a prominent sex interaction (p for interaction with age and systolic BP: 0.004 and 0.028 respectively, where the longitudinal associations of age and systolic BP with increasing CCAD as more pronounced in women than men.These data demonstrated that carotid artery remodeling may parallel subclinical biomarker of cardiac dysfunction, and further showed greater effects of aging and higher blood pressure on such remodeling process in women than men. Further study is warranted to understand how this predisposition of elderly hypertensive women to vascular remodeling may play a role in clinical settings.

  17. Composition of connective tissues and morphometry of vascular smooth muscle in arterial wall of DOCA-salt hypertensive rats - In relation with arterial remodeling.

    Science.gov (United States)

    Hayashi, Kozaburo; Shimizu, Emiko

    2016-05-01

    Hypertension (HT) was induced in Wistar rats aged 16 and 48 weeks by a deoxycortico-sterone acetate (DOCA)-salt procedure. Common carotid arteries were resected 16 weeks after, and their histological specimens were selectively stained for observations of collagen, elastin, and vascular smooth muscle (VSM) cells. Then, the fractions of collagen and elastin and their radial distributions, and the size and number of VSM cells were determined with an image analyzer. These results were compared with the results from age-matched, non-treated, normotensive (NT) animals and also with those from our previous biomechanical studies. In both age groups, there were no significant differences in the fractions of collagen and elastin, and the ratio of collagen to elastin content between HT and NT arteries. These results correspond well with our previous biomechanical results, which showed no significant difference in wall elasticity between HT and NT vessels. Moreover, in the innermost layer out of 4 layers bordered with thick elastic lamellae, the fraction of collagen was significantly greater in HT arteries than in NT ones, which is attributable to HT-related stress concentration in the layer. VSM cells were significantly hypertrophied and their content was increased by HT, although their total number in the media remained unchanged. The increased size and content of cells correspond to the enhancement of vascular tone and contractility in HT arteries.

  18. Composition of connective tissues and morphometry of vascular smooth muscle in arterial wall of DOCA-salt hypertensive rats - In relation with arterial remodeling.

    Science.gov (United States)

    Hayashi, Kozaburo; Shimizu, Emiko

    2016-05-01

    Hypertension (HT) was induced in Wistar rats aged 16 and 48 weeks by a deoxycortico-sterone acetate (DOCA)-salt procedure. Common carotid arteries were resected 16 weeks after, and their histological specimens were selectively stained for observations of collagen, elastin, and vascular smooth muscle (VSM) cells. Then, the fractions of collagen and elastin and their radial distributions, and the size and number of VSM cells were determined with an image analyzer. These results were compared with the results from age-matched, non-treated, normotensive (NT) animals and also with those from our previous biomechanical studies. In both age groups, there were no significant differences in the fractions of collagen and elastin, and the ratio of collagen to elastin content between HT and NT arteries. These results correspond well with our previous biomechanical results, which showed no significant difference in wall elasticity between HT and NT vessels. Moreover, in the innermost layer out of 4 layers bordered with thick elastic lamellae, the fraction of collagen was significantly greater in HT arteries than in NT ones, which is attributable to HT-related stress concentration in the layer. VSM cells were significantly hypertrophied and their content was increased by HT, although their total number in the media remained unchanged. The increased size and content of cells correspond to the enhancement of vascular tone and contractility in HT arteries. PMID:26987272

  19. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

    Directory of Open Access Journals (Sweden)

    Ana Arnalich-Montiel

    2014-01-01

    Full Text Available The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR. For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min. Age-matched untreated male SHR and Wistar Kyoto rats (WKY were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW, wall-to-lumen ratio (W/L, and media cross-sectional area (MCSA. Dose-response curves for acetylcholine (ACh and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA, nitrites, and total antioxidant capacity (TAC. We observed a significant reduction in WW (P<0.001, W/L (P<0.05, and MCSA (P<0.01 and improved endothelium-dependent relaxation (AUCSHR-E = 201.2±33 versus AUCSHR = 97.5±21, P<0.05 in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6 to 10−4 mol/l for SHR-E with respect to WKY. SOSA (P<0.001 and nitrite (P<0.01 values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR.

  20. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

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    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  1. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

  2. Capabilities of Cluster Analysis in Interpretation of 24-Hour Blood Pressure Monitoring Data in Patients with Arterial Hypertension and Left Ventricular Remodeling

    Directory of Open Access Journals (Sweden)

    S.V. Samoyavcheva

    2015-12-01

    Full Text Available The aim of the investigation was to assess the potential of cluster analysis as an additional method of data analysis for 24-hour blood pressure monitoring (BPM in patients with both normal geometry and with various types and extents of remodeling of the left ventricle (LV. Materials and Methods. The investigation included 71 patients, ranging in age from 23 to 71. The inclusion criterion was significant arterial hypertension (AH, while exclusion criteria were symptomatic AH and severe co-morbidity. Body mass, height, waist measurement, body mass index, lipid profile, and glycemic level were determined for each subject in addition to carrying out echocardiography and conventional and cluster analysis of 24-hour BPM data of each. Results. In patient groups with different types of left ventricular hypertrophy (LVH, the conventional analysis demonstrated differences in the standard 24-hour BPM parameters. Development of concentric LVH is associated with the highest average day-time and average night-time blood pressure, pressure-induced loads and blood pressure variability. Eccentric LVH has a pathogenetic link to other factors and is formed under conditions of relatively low blood pressure. The use of cluster analysis allowed to reveal the increased occurrence of systolic-diastolic AH in concentric LVH, and isolated systolic AH and isolated diastolic AH in eccentric LVH. Conclusion. Such an integrated approach to the interpretation of 24-hour BPM results, comprising both conventional and cluster analysis, allows for objectification of the study results and reveals the significant features of AH in patients with different types of LV remodeling.

  3. Conjugated agent insulin-antisense-c-myb-PS-ODN enhances the inhibitory effect on proliferation of rat aortic artery smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM:Vascular smooth muscle cell (SMC) proliferation and migration from the arterial wall media into the intima are believed to play a critical role in the pathogenesis of restenosis. Several studies have demonstrated that phosphothioate (PS) oligodeoxynucleotides targeted against genes involved in SMC proliferation inhibits in vitro SMC proliferation and migration. However, the therapeutic effect of antisense ODN on the individual who receives the treatment of delivery of the agent depends on the efficacy of this agent in great degree. We investigated the inhibition effect of a novel agent, insulin-antisense-c-myb-PS-ODN on SMC proliferation in vitro. METHODS:The rat aortic artery SMCs were cultured in Dulbecco's modified Eagel's medium. The passage 8 to 13 were used as the experiment. Cell surface receptor binding assay was quantified through counting gamma particles emitted from 125    I labeled insulin. SMC rapid proliferation was brought by stimulation of high concentration of fetal bovine serum (FBS). The novel agent of insulin conjugated to the antisense-c-myb-PS-ODN was obtained via incubation of both in condition of certain reagents, pH, temperature, and ion concentration. The characterization and purification of the agent was performed through HPLC. Inhibition of SMC proliferation was reflected by incorporation rate of trillium labeled thymidine deoxyribonucleotide.RESULTS:The binding efficacy of insulin to the receptor was remarkably increased in SMC cultured in supplement of 20% FBS. The inhibition effect of conjugator insulin-c-myb-antisense-PS-ODN was stronger than that of the simple c-myb-antisense-PS-ODN. The inhibition rate of conjugator and simple form on SMC proliferation were 48.34% and 29.54%, respectively. CONCLUSION:The binding efficacy and specificity of c-myb-antisense-PS-ODN to SMC may be enhanced by the insulin receptor mediation through the insulin-insulin receptor interaction. The insulin-receptor targeted method may be a

  4. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration

    OpenAIRE

    Chujo, Yoshikazu; Fujii, Namiki; Okita, Naoyuki; Konishi, Tomokazu; Narita, Takumi; Yamada, Atsushi; Haruyama, Yushi; Tashiro, Kosuke; Chiba, Takuya; Shimokawa, Isao; Higami, Yoshikazu

    2012-01-01

    The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adipose tissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6–7-month-old wild-type Wistar rats fed ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although ...

  5. Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia.

    Science.gov (United States)

    Nakabayashi, Yasushi; Nakashima, Akitoshi; Yoshino, Osamu; Shima, Tomoko; Shiozaki, Arihiro; Adachi, Tomoko; Nakabayashi, Masao; Okai, Takashi; Kushima, Miki; Saito, Shigeru

    2016-04-01

    In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data have shown that impaired autophagy of extravillous trophoblasts (EVT) may induce poor vascular remodeling in preeclampsia. We have studied the distribution of T cells, NK cells and macrophages in the decidua basalis of 14 normotensive OD pregnancies, 5 preeclamptic OD cases, 16 normotensive pregnancy cases, and 13 preeclamptic cases in natural pregnancy or autologous oocyte IVF-ET (NP/IVF). The populations of decidual CD3(+)T cells, CD8(+)T cells, CD4(+)T cells, Foxp3(+)Treg cells, CD56(+)NK cells, and CD68(+) macrophages in preeclampsia were significantly smaller than those in normal pregnancy in NP/IVF. Those frequencies in normotensive OD pregnancies or preeclamptic cases in OD pregnancies were similar to those in preeclamptic cases in NP/IVF. Impaired vascular remodeling was observed in OD pregnancies, regardless of the presence or absence of preeclampsia. The expression of p62, an impaired autophagy marker in EVT of normotensive or preeclamptic OD pregnancies, was significantly higher than that in normal pregnancies in NP/IVF. Immunological change in the decidua basalis and impairment of autophagy in EVT may induce impairment of spiral artery remodeling in OD pregnancies. PMID:26282090

  6. Superior Mesenteric Artery Syndrome Complicated by Diabetic Ketoacidosis and Graves' Disease in Slowly Progressive Insulin Dependent Diabetes Mellitus (SPIDDM): A Case Report and a Review of the Literature.

    Science.gov (United States)

    Hirai, Hiroyuki; Fukushima, Naotaro; Hasegawa, Koji; Watanabe, Tsuyoshi; Hasegawa, Osamu; Satoh, Hiroaki

    2016-01-01

    A 48-year-old woman with a history of diabetes was admitted for nausea and vomiting with body weight loss. A blood examination revealed high plasma glucose and thyroid hormone levels and metabolic acidosis. She was therefore diagnosed with both diabetic ketoacidosis (DKA) and hyperthyroidism. Nausea and vomiting continued intermittently despite the administration of saline and insulin. The patient was further diagnosed with superior mesenteric artery syndrome (SMAS) after abdominal computed tomography revealed that a horizontal portion of the duodenum was sandwiched between the aorta and the superior mesenteric artery. Clinicians should be vigilant for SMAS in patients with both DKA and hyperthyroidism who present body weight loss. PMID:27477411

  7. Remodeling of Aorta Extracellular Matrix as a Result of Transient High Oxygen Exposure in Newborn Rats: Implication for Arterial Rigidity and Hypertension Risk

    Science.gov (United States)

    Castro, Michele M.; Cloutier, Anik; Bertagnolli, Mariane; Sartelet, Hervé; Germain, Nathalie; Comte, Blandine; Schulz, Richard; DeBlois, Denis; Nuyt, Anne Monique

    2014-01-01

    Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory. PMID:24743169

  8. Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk.

    Directory of Open Access Journals (Sweden)

    Fanny Huyard

    Full Text Available Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory.

  9. Role of neural NO synthase (nNOS uncoupling in the dysfunctional nitrergic vasorelaxation of penile arteries from insulin-resistant obese Zucker rats.

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    Ana Sánchez

    Full Text Available OBJECTIVE: Erectile dysfunction (ED is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR, an experimental model of metabolic syndrome/prediabetes. METHODS AND RESULTS: Electrical field stimulation (EFS under non-adrenergic non-cholinergic (NANC conditions evoked relaxations that were significantly reduced in penile arteries of OZR compared with those of lean Zucker rats (LZR. Blockade of NO synthase (NOS inhibited neural relaxations in both LZR and OZR, while saturating concentrations of the NOS substrate L-arginine reversed the inhibition and restored relaxations in OZR to levels in arteries from LZR. nNOS expression was unchanged in arteries from OZR compared to LZR and nNOS selective inhibition decreased the EFS relaxations in LZR but not in OZR, while endothelium removal did not alter these responses in either strain. Superoxide anion production and nitro-tyrosine immunostaining were elevated in the erectile tissue from OZR. Treatment with the NADPH oxidase inhibitor apocynin or acute incubation with the NOS cofactor tetrahydrobiopterin (BH4 restored neural relaxations in OZR to levels in control arteries, while inhibition of the enzyme of BH4 synthesis GTP-cyclohydrolase (GCH reduced neural relaxations in arteries from LZR but not OZR. The NO donor SNAP induced decreases in intracellular calcium that were impaired in arteries from OZR compared to controls. CONCLUSIONS: The present study demonstrates nitrergic dysfunction and impaired neural NO signalling due to oxidative stress and nNOS uncoupling in penile arteries under conditions of insulin

  10. Altered Daytime Fluctuation Pattern of Plasminogen Activator Inhibitor 1 in Type 2 Diabetes Patients with Coronary Artery Disease: A Strong Association with Persistently Elevated Plasma Insulin, Increased Insulin Resistance, and Abdominal Obesity

    Directory of Open Access Journals (Sweden)

    Katarina Lalić

    2015-01-01

    Full Text Available This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D patients with coronary artery disease (CAD (group A, 10 T2D patients without CAD (group B, 12 nondiabetics with CAD (group C, and 12 healthy controls (group D. The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P<0.05 and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; P<0.001. HOMA-IR was higher in group A versus group B (P<0.05 and in C versus D (P<0.01. Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B (P<0.05 and in C versus D (P<0.01, while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis.

  11. Induction of insulin resistance by high-sucrose feeding does not raise mean arterial blood pressure but impairs haemodynamic responses to insulin in rats.

    Science.gov (United States)

    Santuré, Marta; Pitre, Maryse; Marette, André; Deshaies, Yves; Lemieux, Christian; Larivière, Richard; Nadeau, André; Bachelard, Hélène

    2002-09-01

    1. This study was undertaken to further investigate the effects of a sucrose-enriched diet on vascular function and insulin sensitivity in rats. 2. Male Sprague-Dawley rats were randomized to receive a sucrose- or regular rat chow-diet for 4 weeks. A first group of sucrose- and chow-fed rats was instrumented with pulsed Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, regional blood flows and insulin sensitivity in conscious rats. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles by using the glucose analogue [(3)H]-2-deoxy-D-glucose. A second group of sucrose- and chow-fed rats was used to obtain information regarding nitric oxide synthase (NOS) isozymes protein expression in muscles, and determine endothelin content in vascular tissues isolated from both dietary groups. 3. Sucrose feeding was found to induce insulin resistance, but had no effect on resting blood pressure, heart rate, or regional haemodynamics. This insulin resistance was accompanied by alteration in the vascular responses to insulin. Insulin-mediated skeletal muscle vasodilation was impaired, whereas the mesenteric vasoconstrictor response was potentiated in sucrose-fed rats. A reduction in eNOS protein content in muscle and an increase in vascular endothelin peptide were noted in these animals. Moreover, a reduction in insulin-simulated glucose transport activity was also noted in muscles isolated from sucrose-fed rats. 4. Together these data suggest that a cluster of metabolic and haemodynamic abnormalities occur in response to the intake of simple sugars in rats.

  12. Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation

    DEFF Research Database (Denmark)

    Barres, Romain; Grémeaux, Thierry; Gual, Philippe;

    2006-01-01

    APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays...

  13. Relationship Between Pulmonary Artery Smooth Muscle Cells and Mechanism of Hypoxia-induced Pulmonary Vascular Remodeling%肺动脉平滑肌细胞与低氧性肺血管重塑形成机制

    Institute of Scientific and Technical Information of China (English)

    张凌云

    2013-01-01

    低氧条件下肺血管收缩、重塑,继而导致肺血管的持续对抗,其中以中膜增厚为主的肺血管重塑是导致低氧性肺动脉高压持续不可逆性病理改变的重要因素.肺动脉平滑肌细胞是肺动脉中膜的主要构成部分,慢性缺氧条件下由于各种活性介质及细胞生长因子稳态的失衡,肺动脉平滑肌细胞聚集、增殖、肥大及分泌胞外基质;另外,肺动脉平滑肌细胞通过各种信号通路与内膜的内皮细胞及外膜的成纤维细胞相互作用,在低氧性肺血管重塑过程中起着至关重要的作用,本文将对肺动脉平滑肌细胞与低氧性肺血管重塑形成机制的最新研究概况作一综述.%Under conditions of hypoxia generalized vasoconstriction and remodeling of the pulmonary vascular leads to pulmonary vascular persistent resistance. The medial thickening is the main reason of pulmonary vascular remodeling and hypoxic pulmonary artery hypertension, pulmonary artery smooth muscle cells (PASMC) are the principal structure of media, and chronic hypoxia induces the imbalance of vasoactive substances and growth factors. Under this condition, the main medial thickening is believed to be attributable to proliferation, hypertrophy and increased accumulation of PASMC as well as expression of extracellular matrix proteins. Moreover, PASMC has an interaction with endothelial cell of intima and fibroblast of adventitia through multiple signal pathways and plays a crucial role in the development of pulmonary vascular remodeling. The article will make a summary of latest research on PASMC and mechanism of hypoxic pulmonary vascular remodeling.

  14. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation

    OpenAIRE

    DU, XUELIANG; Edelstein, Diane; Obici, Silvana; Higham, Ninon; Zou, Ming-Hui; Brownlee, Michael

    2006-01-01

    Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals...

  15. Associations of metabolic variables with arterial stiffness in type 2 diabetes mellitus : focus on insulin sensitivity and postprandial triglyceridaemia

    NARCIS (Netherlands)

    van Dijk, RAJM; Bakker, SJL; Scheffer, PG; Heine, RJ; Stehouwer, CDA

    2003-01-01

    Background Type 2 diabetes mellitus is associated with an increased risk of atherothrombotic disease, which may in part be mediated through increased arterial stiffness. We investigated to what extent increased arterial stiffness is associated with cardiovascular risk factors that commonly cluster i

  16. Effect of renin-angiotensin -aldosterone system blockers on myocardial remodeling processes and risk for atrial fibrillation in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2014-07-01

    Full Text Available The given review considers the mechanisms underlying the development and maintenance of atrial fibrillations (AF. It is noted that the processes of atrial fibrosis, ion channel remodeling, inflammation, apoptosis, impaired intercellular interactions, and myocardiocyte hypertrophy may give rise to atrial structural and functional changes in AF. The efficacy of angiotensinonverting enzyme inhibitors and angiotensin receptor antagonists is justified in patients with left ventricular systolic dysfunction.

  17. Efeito da L-arginina na neoproliferação intimal e no remodelamento arterial após lesão por balão, em ilíacas de coelhos hipercolesterolêmicos The effect of L-arginine on neointimal proliferation and artery remodeling on an iliac artery lesion caused by a balloon catheter in hypercholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    José Knopfholz

    2006-10-01

    Full Text Available OBJETIVO: A neoproliferação intimal e o remodelamento têm sido implicados como os maiores fatores causadores de reestenose. O objetivo deste trabalho é estudar a ação da L-arginina por via oral, nesses dois fatores, após lesão por balão, em artérias ilíacas de coelhos hipercolesterolêmicos. MÉTODOS: Foram utilizados dezenove coelhos, que foram divididos em dois grupos: controle (GC e arginina (GA, respectivamente com dezenove e dezessete artérias estudadas. Os animais foram submetidos a lesão por balão de angioplastia, em suas artérias ilíacas, quinze dias após início de dieta hipercolesterolêmica a 2%. A seguir, os animais do GA passaram a receber uma solução de L-arginina, por via oral, na dose de 1 g/kg/dia. Após o sacrifício, no 15º dia após a lesão por balão, procedeu-se a cortes histológicos das artérias, as quais foram coradas e fixadas. Utilizou-se como representativa do desenvolvimento da lesão a razão da área da neoíntima (em mm² pela camada média (em mm². Por sua vez, a razão da área total do vaso em sua porção medial (de maior contato com o balão pela área total do vaso no segmento referencial (de menor contato com o balão foi a definidora do remodelamento. RESULTADOS: A média do espessamento neointimal (NI/M foi de 0,8151±0,2201 no GC e de 0,3296±0,1133 no GA. Não houve diferença entre os tipos de remodelamento entre os dois grupos estudados. CONCLUSÃO: No modelo experimental utilizado, a L-arginina foi capaz de reduzir o espessamento intimal em coelhos hipercolesterolêmicos e não teve ação sobre o remodelamento arterial.OBJECTIVE: It has been implied that neointimal proliferation and remodeling are the major causes of restenosis. The objective of this study is to assess the effect of orally administered L-arginine on these two factors in hypercholesterolemic rabbits that had suffered an injury to their iliac arteries caused by a catheter balloon. METHODS: The study included

  18. 胰岛素对大鼠心肌梗死后心室重构和心脏功能的影响及其机制%Effects of insulin on ventricular remodeling and cardiac functions after myocardial infarction and its underlying mechanism

    Institute of Scientific and Technical Information of China (English)

    韦广洪; 付锋; 马斌; 薛洋; 李嘉; 张利华

    2013-01-01

    目的:探讨胰岛素对大鼠心肌梗死(MI)后心室重构和心脏功能的影响及其机制.方法:80只成年雄性Sprague-Dawley大鼠行冠状动脉左前降支(LAD)结扎制备MI模型,随机分为5组:即假手术(Sham)组(n=20)、生理盐水对照(MI+ NS)组(n=20)、胰岛素治疗(MI+ Ins)组(n=20)、肿瘤坏死因子α(TNF-α)拮抗剂益赛普治疗(MI+ En)组(n=10)及Ins+ En治疗(MI+ Ins+ En)组(n=10).用ELISA法检测各组大鼠在MI后1周和4周时,心肌及血清TNF-α的水平.超声心动图测定各组大鼠左室射血分数(EF)、缩短分数(FS)和左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)、经右颈总动脉插管测定血压(BP)、左室舒张压(LVDP)和最大左室舒张压/收缩压变化速率(±LVdp/dtmax).结果:大鼠MI后心肌中TNF-α增加,Ins治疗可明显降低大鼠心肌中TNF-α的含量(P<0.05,n=6).Ins治疗组大鼠EF、FS、LVDP和±LVdp/dtmax均明显高于对照组(P <0.05,n=10),LVESD明显低于对照组(P<0.05,n=10).与单独En治疗组相比,Ins+ En治疗组大鼠EF、FS、LVDP和±LVdp/dtmax明显升高、LVESD明显降低(P <0.05,n=10).结论:Ins可抑制MI后心室的扩张,改善心脏功能,但其机制不依赖于抑制心肌TNF-α的产生.%AIM: To investigate the effect of insulin treatment on ventricular remodeling and cardiac functions after myocardial infarction (MI) and the underlying mechanism. METHODS: MI models were established by ligation of the left anterior descending coronary artery (LAD). Eighty male adult Sprague Dawley rats were randomly divided into five groups: sham (n = 20) , MI + saline ( n = 20) , MI + insulin (n = 20) , MI + etanercept ( n = 10) , and MI + etanercept + insulin ( n = 10 ) . Serum and myocardial tumor necrosis factor-α (TNF-α) were measured at 1 week and 4 weeks after MI. Left ventricular (LV) fractional shortening ( FS) , ejection fraction ( EF) , LV end-diastolic diameter ( LVEDD) and end-systolic diameter (LVESD) were measured

  19. Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

    Directory of Open Access Journals (Sweden)

    Gerová M.

    2005-01-01

    Full Text Available Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh and bradykinin (BK in nitric oxide (NO-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg or pentaerythritol tetranitrate (100 mg/kg, twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01 hypotensive response to ACh (1 and 10 µg, 87.9 ± 6.9 and 108.1 ± 5.1 vs 35.9 ± 4.7 and 64.0 ± 3.3 mmHg, and BK (100 µg, 106.7 ± 8.3 vs 53.3 ± 5.2 mmHg. SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 ± 3.6 vs 74.2 ± 8.6% in controls, P < 0.01. Iliac artery inner diameter also increased (680 ± 46 vs 828 ± 28 µm in controls, P < 0.01. Wall thickness, wall cross-section area, wall thickness/inner diameter ratio increased significantly (P < 0.01. No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NO-deficient hypertension.

  20. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

    Science.gov (United States)

    Mohan, Mohapradeep; McSwiggan, Stephen; Baig, Fatima; Rutherford, Lynn; Lang, Chim C

    2015-02-01

    Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

  1. State of integral remodeling parameters of target organs in patients with essential hypertension and obesity.

    Science.gov (United States)

    Kochueva, M; Sukhonos, V; Shalimova, A; Psareva, V; Kirichenko, N

    2014-06-01

    Arterial hypertension combined with obesity is a very common form of comorbid disease in most countries all over the world. The combination of these diseases is characterized by mutual burdening of remodelling processes in important target organs, what greatly increases the risk of cardiovascular complications and death. The mechanisms of injury progression to vital organs in essential hypertension (EH) and obesity have some common features. The most important risk factors of target organs damage are hemodynamic and neurohumoral: inflammatory, effectors of the renin- angiotensin-aldosterone system, insulin resistance and others. Polyethiologic remodelling, lack of knowledge concerning violations in structural and functional status of important target organs and mechanisms of the interactions of their progression with this comorbidity require further study of these issues. The objective of the study was the comparative study of the state of integral indicators of structural and functional state of the heart, blood vessels and liver in patients with EH second stage with normal body weight and with concomitant obesity I and II degrees. This study found that the presence of obesity I and II in patients with EH stage II is associated with the concentric type of left ventricular hypertrophy, saved by its ejection fraction and impaired diastolic filling processes. For the patients with EH in the early stages of obesity the following characteristics are quite typical: considerable increase of intima media thickness in the carotid arteries, increasing the stiffness in the main arteries and liver parenchyma, impaired of the functional state of endothelial.

  2. 趾动脉终末支岛状皮瓣重塑再造指外形%Toe artery terminal branch island flap for finger reconstruction and remodeling

    Institute of Scientific and Technical Information of China (English)

    巨积辉; 侯瑞兴; 李雷; 李建宁; 刘新益; 周荣; 李祥军; 熊胜; 李秀平; 王盛福

    2011-01-01

    目的 研究趾动脉终末支岛状皮瓣重塑再造指外形的可行性.方法 2008年3月至2009年12月,对17例(19指)手指缺损游离足趾移植再造的患者,术中同时采用足趾趾动脉终末支岛状皮瓣转移嵌入第二趾颈部,消除因该部位狭窄导致的再造指外形的缺陷.结果 术后再造19指及嵌入趾颈部狭窄处皮瓣全部存活,供受区伤口Ⅰ期愈合.随访时间为6~17个月,平均8个月.再造指外形得到明显改善,指腹感觉恢复良好,两点分辨觉为8~12 mm.结论 应用趾动脉终末支岛状皮瓣重塑再造手指外形,解决了再造指指腹膨大和掌侧颈部狭窄的外形缺陷,临床疗效较好.%Objective To study the feasibility of using toe artery terminal branch island flap for remodeling and reconstruction of finger shape. Methods From March 2008 to December 2009,19 fingers of 17 cases that were reconstructed by toe transfer had the toe artery terminal branch island flap inserted in the neck of the second toe during the toe transfer surgery to correct the appearance deficit caused by the narrow area. Results All 19 reconstructed fingers and the inserted toe artery terminal branch island flaps survived after the surgery. Donor site wound had primary healing. Postoperative follow-up lasted 6 to 17 months,with an average of 8 months. The appearance of reconstructed fingers was greatly improved. There was good recovery of pulp sensation,with two-point discrimination being 8 to 12 mm. Patients feel quite satisfied. Conclusion Toe artery terminal branch island flap corrects the deficit in appearance of fingers the palm side of the finger.

  3. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

    OpenAIRE

    Arnalich-Montiel, Ana; González, María Carmen; Delgado-Baeza, Emilio; Delgado-Martos, María Jesús; Condezo-Hoyos, Luis; Martos-Rodríguez, Antonia; Rodríguez-Rodríguez, Pilar; Quintana-Villamandos, Begoña

    2014-01-01

    The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300  μ g/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coro...

  4. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

    OpenAIRE

    Ana Arnalich-Montiel; María Carmen González; Emilio Delgado-Baeza; María Jesús Delgado-Martos; Luis Condezo-Hoyos; Antonia Martos-Rodríguez; Pilar Rodríguez-Rodríguez; Begoña Quintana-Villamandos

    2014-01-01

    The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR andWistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyz...

  5. Determination of arterial wall shear stress

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The arteries can remodel their structure and function to adapt themselves to the mechanical environment. In various factors that lead to vascular remodeling, the shear stress on the arterial wall induced by the blood flow is of great importance. However, there are many technique difficulties in measuring the wall shear stress directly at present. In this paper, through analyzing the pulsatile blood flow in arteries, a method has been proposed that can determine the wall shear stress quantitatively by measuring the velocity on the arterial axis, and that provides a necessary means to discuss the influence of arterial wall shear stress on vascular remodeling.

  6. The Associations of High-Density Lipoprotein Subclasses With Insulin and Glucose Levels, Physical Activity, Resting Heart Rate, and Regional Adiposity in Men With Coronary Artery Disease: The Stanford Coronary Risk Intervention Project Baseline Survey

    OpenAIRE

    Williams, Paul T.; Haskell, William L; Vranizan, Karen M; Ronald M. Krauss

    1995-01-01

    We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was used as an index of mass concentrations at interv...

  7. Coronary microvascular function, insulin sensitivity and body composition in predicting exercise capacity in overweight patients with coronary artery disease

    DEFF Research Database (Denmark)

    Jürs, Anders; Pedersen, Lene Rørholm; Olsen, Rasmus Huan;

    2015-01-01

    BACKGROUND: Coronary artery disease (CAD) has a negative impact on exercise capacity. The aim of this study was to determine how coronary microvascular function, glucose metabolism and body composition contribute to exercise capacity in overweight patients with CAD and without diabetes. METHODS...... by a cardiopulmonary exercise test. Body composition was determined by whole body dual-energy X-ray absorptiometry scan and magnetic resonance imaging. Coronary flow reserve (CFR) assessed by transthoracic Doppler echocardiography was used as a measure of microvascular function. RESULTS: Median BMI was 31.3 and 72...... metabolism and body composition. CFR, EDV and LVEF remained independent predictors of VO2peak in multivariable regression analysis. CONCLUSION: The study established CFR, EDV and LVEF as independent predictors of VO2peak in overweight CAD patients with no or only mild functional symptoms and a LVEF > 35...

  8. Growth hormone and insulin-like growth factor-1 in prognosis coronary artery disease in patients with obesity

    Directory of Open Access Journals (Sweden)

    Olga Viktorovna Shpagina

    2014-10-01

    Full Text Available Introduction. In patients with obesity coronary atherosclerosis and chronic heart failure (CHF progress rapidly and have a worse long-term prognosis than those with normal weight.Objective: To investigate the prognostic significance of GH and IGF-1 in the evaluation of cardiovascular risk in patients with obesity.Materials and Methods. The study included 75 men (mean age 55.31±6.32 years, which are overweight or have mild obesity (body mass index (BMI 28.69±3.6 kg/m2. Group 1 included 45 patients (age 56.4±6.29 years, BMI 28.69±3.69 kg/m2, blood pressure 124±10.18/80±4.59 mm Hg who underwent coronary angiography. Group 2 included 30 patients (mean age 53.6 ± 6.1 years, BMI 28.68±3.52 kg/m2, blood pressure 128±9/83±6.81 mm Hg, CAD who are excluded by treadmill test. The coronary artery calcium score was assessed in group 2. All participants were evaluated impaired glucose tolerance (IGT, triglycerides (TG, IGF-1 and GH, LPHD, LPLD, geometry of the heart chambers was assessed by echocardiography.Results. Patients in both groups did not differ in age, BMI, blood pressure. IGF-1 levels were not significantly different among the study groups. High circulating IGF-1 levels were frequently observed in group 1 (р=0.018. A statistically significant association of high IGF-1 observed with obesity (p=0.033, smoking (p=0.049, hypertension (p=0.002, end-diastolic dimension (p=0.045. GH was lower in group 1 compared with group 2 (p=0.046. Serum levels of GH are positively associated with EF (p=0.023 and E/A (p=0.043 and negatively associated with left atrial wall thickness (p=0.025 and coronary artery calcium score (p=0.005.Conclusion: 1. IGF-1 may be a useful indicator to assess the prognosis of CAD and CHF in patients with obesity. 2. Relative GH deficiency was more often associated with severe CAD in patients with obesity.

  9. Vascular Function, Insulin Action and Exercise: An Intricate Interplay

    OpenAIRE

    Zheng, Chao; Liu, Zhenqi

    2015-01-01

    Insulin enhances the compliance of conduit arteries, relaxes resistance arterioles to increase tissue blood flow and dilates precapillary arterioles to expand muscle microvascular blood volume. These actions are impaired in the insulin resistant states. Exercise ameliorates endothelial dysfunction and improves insulin responses in insulin resistant patients, but the precise underlying mechanisms remain unclear. The microvasculature critically regulates insulin action in muscle by modulating i...

  10. 卡维地洛对大鼠颈动脉损伤后血管重塑的影响%Effect of carvedilol on vascular remodeling in carotid artery-injured rats

    Institute of Scientific and Technical Information of China (English)

    袁向珍; 刘敏; 曹中朝; 包秋红

    2015-01-01

    目的:探讨卡维地洛(carvedilol,CAR)对大鼠颈动脉损伤后血管重塑的影响.方法:雄性Wistar大鼠90只,随机分为假手术组、损伤组和CAR组,后两组行颈动脉球囊损伤术.三组均于术后1、3、7、14、28天处死大鼠.光镜下观察血管损伤后内膜增生情况,用免疫组化和RT-PCR法检测MMP-2、MMP-9和TIMP-1在各组术后不同时间点的表达情况.结果:与损伤组比较,术后14dCAR组内膜面积、内膜与中膜面积比值显著减少,管腔面积显著扩大(P0.05).结论:卡维地洛有效抑制大鼠颈动脉损伤后MMP-2和MMP-9表达,改善了细胞外基质的合成与降解平衡,抑制血管重塑,减轻再狭窄.%Objective: To explore the effect of carvedilol (CAR) on vascular remodeling in carotid artery-injured rats. Methods:Ninety Wistar rats were randomly divided into sham-operated group, injury group and CAR group, and the model of carotid baloon injury were established in the latter two groups. The rats were kiled on the 1st、3rd、7th、14th、28th day after injury. The intimal proliferation was observed by optical microscope. The expression of MMP-2, MMP-9 and TIMP-1 at different time points was detected by the method of immunohistochemistry and RT-PCR. Results:The intimal area (IA) and ratio of intimal and medial area (IA/MA)in CAR group were signiifcantly lower than those in injury group, while lumen area was higher than its in injury group (P<0.05). Compared to injury group, the expression of MMP-2 and MMP-9 significantly decreased in CAR group on the 3rd to 14th day after injury (P<0.05), while the expression of TIMP-1 had no difference between two groups.Conclusion: CAR could inhibit vascular remodeling and reduce restenosis, the mechanism of which may inhibit the expression of MMP-2 and MMP-9 in carotid artery-injured rats, improve balance of synthesis and degradation of extracellular matrix.

  11. Influence of insulin resistance on long-term outcomes in patients with coronary artery disease after sirolimus-eluting stent implantation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Liang-ping; L(U) An-kang; SHEN Wei-feng; LIU Hai-feng; MA Xiao-ye; FAN Xiao-ming; ZHANG Qi

    2010-01-01

    Background Insulin resistance(IR)is significantly associated with coronary artery disease and cardiovascular events in patients with or without type 2 diabetes mellitus.This study aimed to evaluate the influence of IR on long-term outcomes of patients undergoing percutaneous coronary intervention(PCI)with sirolimus-eluting stent(SES)implantation.Methods A total of 467 consecutive patients undergoing SES-based PCI were divided into lR group(n=104)and non-IR group(n=363).The patients were followed up for one year.The rate of major adverse cardiac events(MACEs) including death, non-fatal myocardial infarction and recurrent angina pectoris was compared by the log-rank test,and the independent risk factors were identified by the Cox regression analysis.Results MACEs occurred more frequently,and cumulative survival rate was lower in the IR group than in the non-IR group during the follow-up (all P<0.05).IR was an independent risk factor for the occurrence of cardiac death and non-fatal myocardial infarction(OR=2176,95% CI=1.35-5.47,P=0.034).Old age,diabetes,and multi-vessel disease were determinants for recurrent angina pectoris after PCI(P<0.05).Subgroup analysis revealed that IR(OR=3.35,95% CI=1.07-13.59,P=0.013)and multi-vessel disease(OR=2.19,95%CI=1.01-5.14,P=0.044)were independent risk predictors for recurrent angina pectoris in patients with diabetes after PCI.Conclusions IR is associated with reduced MACE-free survival and remains an independent predictor for recurrent angina pectoris after PCI with SES implantation.

  12. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  13. Insulin Secretagogues

    Science.gov (United States)

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  14. Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension%肾去交感神经对肺动脉高压模型犬肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    张淑娟; 赵庆彦; 蒋学俊; 杨波; 代子玄; 王晓占; 王徐乐; 郭宗文; 于胜波

    2015-01-01

    目的 探讨肾去交感神经(RSD)对肺动脉高压(PAH)模型犬肺血管重构的影响.方法 24只比格犬按随机数字表法随机均分为对照组、PAH组、PAH+ RSD组各8只.检测各组犬实验前血清神经激素水平、心脏超声和血流动力学参数后,对照组右心房注入二甲基甲酰胺(0.1 ml/kg),PAH组右心房注入脱氢野百合碱(2 ml/kg),PAH+ RSD组先行肾去交感神经术,后右心房注入脱氢野百合碱(2 ml/kg).喂养8周,检测各组犬实验后的血清神经激素水平、心脏超声和血流动力学参数后,开胸取肺组织检测肺血管形态学.结果 实验后PAH组、PAH+ RSD组右心室收缩压(RVSP)和肺动脉收缩压(PASP)均显著高于对照组[(42.8±8.7)、(30.8±6.8)比(23.2±5.7) mmHg(1mmHg =0.133 kPa)和(45.1±11.2)、(32.6±7.9)比(24.7 ±7.1)mmHg],且PAH组RVSP和PASP显著高于PAH+ RSD组[均P<0.01].实验后PAH组血清血管紧张素Ⅱ(AngⅡ)和内皮素1水平均显著高于实验前[(228 ±41)比(113±34) pg/ml和(135 ±15)比(77±7)pg/ml,均P<0.01],且肺组织中AngⅡ和内皮素1水平[(65±10)和(96±10)pg/ml]均显著高于对照组[(38±7)和(54±6)pg/ml]和PAH+ RSD组[(46±8)和(67±9)pg/ml](均P<0.01).与对照组相比,PAH组肺泡2型细胞破坏严重,组织纤维化明显,而PAH+ RSD组肺泡2型细胞破坏及组织纤维化较PAH组轻.结论 RSD可降低PAH模型犬肺动脉高压并抑制肺血管重构,此作用可能与其降低神经激素水平有关.%Objective To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH).Methods According to the random number table,24 beagles were randomized into control,PAH and PAH + RSD groups (n =8 each).The levels of neurohormone,echocardiogram and dynamics parameters were measured.Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH + RSD groups) were injected.The PAH + RSD group

  15. Insulin and Insulin Resistance

    OpenAIRE

    Wilcox, Gisela

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, stru...

  16. A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease

    DEFF Research Database (Denmark)

    Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Jürs, Anders;

    2015-01-01

    difference between the groups (pvisceral abdominal fat, waist circumference and body weight. Intention-to-treat analyses (n=64......) yielded similar results. CONCLUSION: LED is superior to AIT in improving insulin sensitivity in prediabetic CAD patients. Changes in insulin sensitivity are associated with decreased visceral abdominal fat, waist circumference and body weight....

  17. Insulin Test

    Science.gov (United States)

    ... especially as a result of taking non-human (animal or synthetic) insulin, these can interfere with insulin testing. In this case, a C-peptide may be performed as an alternative way to evaluate insulin production. Note also that ...

  18. Remodeling Pattern of Atherosclerotic Middle Cerebral Artery Stenosis on 3.0T High-Resolution Magnetic Resonance Imaging%3.0T高分辨磁共振研究大脑中动脉粥样硬化性狭窄重构模式

    Institute of Scientific and Technical Information of China (English)

    朱先进; 王春雪; 姜卫剑; 杜彬; 金旻; 娄昕; 马林

    2013-01-01

    Objective To investigate the remodeling pattern of symptomatic atherosclerotic middle cerebral artery(MCA) stenosis with 3.0T high-resolution magnetic resonance imaging(HRMRI). Methods Eighty-seven consecutive patients with symptomatic atherosclerotic stenoses at M1 segment of MCA on digital subtraction angiography(DSA)(50%-99%) were enrolled from November 2009 to May 2011. HRMRI was performed on the target segment by using a 3.0T MR scanner. Remodeling index(RI) was calculated as vessel area at maximal lumen narrowing(MLN)/reference vessel area. RI≤0.95 was defined as negative remodeling(NR), RI≥1.05 as positive remodeling(PR), and 0.95>RI<1.05 as intermediate remodeling(IR). Wall characteristics were compared between the NR and PR group. Results Seventy patients were included in the final analysis, and NR was found in 29(41.4%) patients, IR in 6(8.6%) patients, and PR in 35(50.0%) patients. At MLN sites, compared with lesions with PR, lesions with NR had a less wall area([11.5±3.0]mm2 vs [16.6±4.5]mm2, P﹤0.001), and percent plaque burden([9.5±17.3]%vs [42.3±11.0]%, P﹤0.001). Conclusion HRMRI can help assess the remodeling pattern of MCA stenosis. In patients with MCA atherosclerotic stenosis, NR lesions are also frequently observed and have a less wall area and plaque burden than PR lesions.%  目的应用3.0T高分辨磁共振成像(high resolution magnetic resonance imaging,HRMRI)探讨症状性大脑中动脉(middle cerebral artery,MCA)粥样硬化性狭窄的重构模式.方法2009年11月~2011年5月连续入组经数字减影血管造影证实的症状性MCA M1段动脉粥样硬化性狭窄(50%~99%)患者87例,使用3.0T磁共振扫描仪对狭窄段进行HRMRI检查,测量并计算重构指数(remodeling index,RI)(最窄处血管面积/参考血管面积).RI≤0.95为阴性重构,RI≥1.05为阳性重构,RI在0.95~1.05之间为无重构.比较阴性重构和阳性重构病变的管壁特点.结果本研究70例患者纳入

  19. Metabolic remodeling in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Tao GUO

    2013-01-01

    Although the management of chronic heart failure (CHF) has made enormous progress over the past decades,CHF is still a tremendous medical and societal burden.Metabolic remodeling might play a crucial role in the pathophysiology of CHF.The characteristics and mechanisms of metabolic remodeling remained unclear,and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability.In the early phases of the disease,metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation.Along with the progress of the disease,the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation.In addition,a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.

  20. Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet

    OpenAIRE

    Yongming, Pan; Zhaowei, Cai; Yichao, Ma; Keyan, Zhu; Liang, Chen; Fangming, Chen; Xiaoping, Xu; Quanxin, Ma; Minli, Chen

    2015-01-01

    Background A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. Methods Male Tibetan minipigs were ...

  1. Mechanism of the Susceptibility of Remodeled Pulmonary Vessels to Drug‐Induced Cell Killing

    OpenAIRE

    Ibrahim, Yasmine F.; Wong, Chi‐Ming; Pavlickova, Ludmila; Liu, Lingling; Trasar, Lobsang; Bansal, Geetanjali; Suzuki, Yuichiro J.

    2014-01-01

    Background Pulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension. Methods and Results...

  2. 缬沙坦对野百合碱诱导肺动脉高压模型大鼠肺动脉重构的影响%Effects of Valsartan on pulmonary arterial remodeling in rats with pulmonary hypertension induced by monocrotaline

    Institute of Scientific and Technical Information of China (English)

    文宏; 李醒三; 陆永光

    2011-01-01

    Objective To explore the effects of valsartan on pulmonary arterial remodeling in rats with pulmonary hypertension induced by monocrotaline. Methods The healthy male Wistar rats were randomly divided into 3 groups : M group (model of pulmonary hypertension) , were given a single suhcutaneous injection ofmonocrotaline (60 mg/kg) at the back, then free feeding and drinking ; Valsartan group were injected with monocrotaline as group M and kept feeding under the same conditions , after 4 weeks with valsartan (20 mg/kg·d) orally for 4 weeks up to the end of the experiment ; control group ( group C) were injected with equivalent saline at the back and kept feeding under the same conditions. Then mean pulmonary artery pressure (mPAP) of the rats was measured by the micro-catheter; the index of the right ventricular hypertrophy was calculated [RV/(LV + S) ] ; with HE staining, elastic fiher staining and VG staining to ohserve pulmonary artery structural changes , calculate the pulmonary artery wall thickness and lumen area and evaluate valsartan on pulmonary artery remodeling. Results Valsartan can reduce the wall thickness and enlarge the wall area of pulmonary arterial in rats with the injection of monocrotaline (P < 0.01). Conclusion Valsartan can inhibit the pulmonary arterial remodeling in rats with pulmonary hypertension , the mechanism maybe related to the inhibition of proliferation meditated by angiotensin Ⅱ.%目的:观察缬沙坦(valsartan)对野百合碱(monocrotaline)所致肺动脉高压大鼠肺血管重构的影响.方法:将健康雄性Wistar 大鼠随机分为3 组:M 组(肺动脉高压模型组)一次性项背部注射野百合碱(60 mg / kg)后自由摄食、饮水;V 组(缬沙坦干预组),同M 组注射野百合碱并同等条件饲养,4 周后开始用缬沙坦20 mg / (kg·d)灌胃,持续4 周达实验终点;C 组(正常对照组)一次性项背部注射等量生理盐水后与实验组同等条件饲养.然后经微导管介入测定大鼠肺

  3. Insulin Signaling and Heart Failure.

    Science.gov (United States)

    Riehle, Christian; Abel, E Dale

    2016-04-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin-resistant states such as type 2 diabetes mellitus and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes mellitus alters the systemic and neurohumoral milieu, leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead box O transcriptional signaling or glucose transport, which may also impair cardiac metabolism, structure, and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed.

  4. Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

    Directory of Open Access Journals (Sweden)

    C.A. Mourão-Júnior

    2006-04-01

    Full Text Available Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI, waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001 after the addition of metformin (1404.4 ± 565.5 mg/day, with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05 of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/dL, BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m², waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm, and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01% and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

  5. Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity.

    Science.gov (United States)

    Bender, Shawn B; Castorena-Gonzalez, Jorge A; Garro, Mona; Reyes-Aldasoro, Constantino C; Sowers, James R; DeMarco, Vincent G; Martinez-Lemus, Luis A

    2015-08-15

    Increased central vascular stiffening, assessed in vivo by determination of pulse wave velocity (PWV), is an independent predictor of cardiovascular event risk. Recent evidence demonstrates that accelerated aortic stiffening occurs in obesity; however, little is known regarding stiffening of other disease-relevant arteries or whether regional variation in arterial stiffening occurs in this setting. We addressed this gap in knowledge by assessing femoral PWV in vivo in conjunction with ex vivo analyses of femoral and coronary structure and function in a mouse model of Western diet (WD; high-fat/high-sugar)-induced obesity and insulin resistance. WD feeding resulted in increased femoral PWV in vivo. Ex vivo analysis of femoral arteries revealed a leftward shift in the strain-stress relationship, increased modulus of elasticity, and decreased compliance indicative of increased stiffness following WD feeding. Confocal and multiphoton fluorescence microscopy revealed increased femoral stiffness involving decreased elastin/collagen ratio in conjunction with increased femoral transforming growth factor-β (TGF-β) content in WD-fed mice. Further analysis of the femoral internal elastic lamina (IEL) revealed a significant reduction in the number and size of fenestrae with WD feeding. Coronary artery stiffness and structure was unchanged by WD feeding. Functionally, femoral, but not coronary, arteries exhibited endothelial dysfunction, whereas coronary arteries exhibited increased vasoconstrictor responsiveness not present in femoral arteries. Taken together, our data highlight important regional variations in the development of arterial stiffness and dysfunction associated with WD feeding. Furthermore, our results suggest TGF-β signaling and IEL fenestrae remodeling as potential contributors to femoral artery stiffening in obesity.

  6. Early Onset Inflammation in Pre-Insulin-Resistant Diet-Induced Obese Rats Does Not Affect the Vasoreactivity of Isolated Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Raun, Kirsten; Boonen, Harrie C M;

    2012-01-01

    Background: Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction....... Our study aimed to investigate signs of inflammation and their relation to vascular dysfunction in rats receiving a high fat diet. Methods: Diet-induced obese (DIO) rats were used as a model since these rats exhibit a human pre-diabetic pathology. Oral glucose and insulin tolerance tests were...... concomitant vascular dysfunction. The results show that inflammation and obesity are tightly associated, and that inflammation is manifested prior to significant insulin resistance and vascular dysfunction....

  7. Efeitos da suplementação de potássio via sal de cozinha sobre a pressão arterial e a resistência à insulina em pacientes obesos hipertensos em uso de diuréticos Effects of potassium supplementation by salt on arterial blood pressure and insulin resistance in hypertensive obese patients on diuretic therapy

    Directory of Open Access Journals (Sweden)

    Maria Alice de Gouveia Pereira

    2005-02-01

    Full Text Available OBJETIVO: Avaliar os efeitos da suplementação de potássio, por intermédio do sal de cozinha contendo cloreto de potássio, associada à dieta hipocalórica e à atividade física aeróbica, sobre a pressão arterial e índices de resistência à insulina em pacientes hipertensos com obesidade abdominal. MÉTODOS: Estudo prospectivo duplo-cego, randomizado, em 22 pacientes hipertensos com excesso de peso (índice de massa corporal >27kg/m² e controle insatisfatório da pressão arterial durante o uso de diuréticos pressão arterial sistólica >140 e 90 e OBJECTIVE: The objectives of the present study were to evaluate the effects of oral potassium supplementation, associated with a hypocaloric diet and aerobic exercises, on plasma potassium levels, blood pressure and insulin resistance, in centrally obese, not well controlled hypertensive patients on diuretic therapy; waist to hip ratio >0.85 in women, and >0.95 in men; systolic blood pressure >140mmHg and 90mmHg and <105mmHg. METHODS: This was a prospective double-blind randomized study including 22 patients divided in 2 groups: sodium chloride n=10, and potassium chloride n=12. For 12 weeks, each group received cooking salt containing, either 100% sodium chloride, or 50% sodium chloride and 50% potassium chloride. All patients were submitted to a hypocaloric diet and advised to increase their physical activity; a 40-minute walk three times a week. Before and after the study period, all patients were submitted to determinations of body mass index, body composition, waist circumference, sodium and potassium urinary excretions, sodium and potassium serum levels, 24h ambulatory blood pressure monitoring, oral glucose tolerance test with serum insulin measurements at fasting and 120 minutes after glucose load, and serum lipid profile. RESULTS: In both groups, no changes were observed in serum sodium and potassium levels, in blood glucose and insulin levels, insulin resistance indexes and serum

  8. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  9. Insulin Injection

    Science.gov (United States)

    ... or buttocks. Do not inject insulin into muscles, scars, or moles. Use a different site for each ... you are using insulin.Alcohol may cause a decrease in blood sugar. Ask your doctor about the ...

  10. Compensatory Effect between Aortic Stiffening and Remodelling during Ageing.

    Directory of Open Access Journals (Sweden)

    Andrea Guala

    Full Text Available The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases.

  11. Oral Insulin

    OpenAIRE

    Kalra Sanjay; Kalra Bharti; Agrawal Navneet

    2010-01-01

    Abstract Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

  12. Concentrated Arabinoxylan but Not Concentrated Beta-Glucan in Wheat Bread Has Similar Effects on Postprandial Insulin as Whole-Grain Rye in Porto-arterial Catheterized Pigs

    DEFF Research Database (Denmark)

    Christensen, Kirstine Lykke; Hedemann, Mette Skou; Lærke, Helle Nygaard;

    2013-01-01

    The acute glycemic effects of concentrated dietary fibers (DF) versus whole-grain rye were studied in portoarterial catheterized pigs. Two white wheat breads with wheat arabinoxylan (AX) or oat beta-glucan (BG), two rye breads with intact rye kernels (RK) or milled rye (GR), and a low DF white...... min postprandial for AX and GR (74.4 and 129 pmol/min for AX and GR, respectively, compared to 738 pmol/min for WF, P effective in improving insulin economy, suggesting that arabinoxylan from wheat and rye induces similar outcomes in the metabolic...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    International Nuclear Information System (INIS)

    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: → Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. → Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. → Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. → Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  15. 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.

  16. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

    DEFF Research Database (Denmark)

    de Rooij, Susanne R; Dekker, Jacqueline M; Kozakova, Michaela;

    2009-01-01

    of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds...... ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin......OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...

  17. Autonomic disbalance their relationship with the cardiovascular hiperreactivity, the resistance to the insulin and the high blood pressure. Desequilibrio autonómico simpático su relación con la hiperreactividad cardiovascular, la resistencia a la insulina y a la hipertensión arterial

    Directory of Open Access Journals (Sweden)

    Yosvel Curbelo Pérez

    Full Text Available During many years has been debated the paper of the Autonomous Nervous System in the development of the arterial hypertension, in passing it constitutes one of the important theories that physiologists. Recently some authors have involved the activity of that system with the resistance to the insulin and with other important aspects that influence in the appearance of arterial hypertension. The objective of this work is to contribute new theoretical elements that link the changes of the activity of the Autonomous Nervous System with the presence of cardiovascular hipereactivity and sustained arterial hypertension.

    Durante muchos años se ha debatido sobre el papel del Sistema Nervioso Autónomo en el desarrollo de la hipertensión arterial, de paso constituye una de las teorías importantes que plantean fisiólogos y estudiosos. Más recientemente algunos autores han involucrado la actividad de ese sistema con la resistencia a la insulina y con otros aspectos importantes que influyen en la aparición de hipertensión arterial. El objetivo de este trabajo es aportar nuevos elementos teóricos que vinculan los cambios de la actividad del Sistema Nervioso Autónomo con la presencia de hiperreactividad cardiovascular e hipertensión arterial sostenida.

  18. [THE EFFECTIVENESS OF THE CORRECTION OF ENDOTHELIAL DYSFUNCTION AND REMODELING OF THE BRACHIAL ARTERY WITH CONCENTRIC AND ECCENTRIC LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH UNSTABLE ANGINA WITH COMORBID HYPERTENSION].

    Science.gov (United States)

    Denesiuk, E V

    2015-01-01

    The study involved patients with unstable angina (UA), comorbid hypertension (AH), myocardial infarction in 55.5% of cases. Systolic blood pressure was (163.2 ± 1.5) mm Hg. Art., diastolic blood pressure--(101.10 ± 0.67) mm Hg. Art., pulse pressure--(61.1 ± 17.0) mm Hg. Art. Examined patients underwent clinical studies, ECG in 12 conventional leads, echocardiography in M and B modes, Doppler ultrasonography of the brachial artery. To correct the detected change using standard combined therapy: perindopril 5-10 mg/day, bisoprolol--5-10 mg/day, atorvastatin--20 mg/day, acetylsalicylic acid--75-100 mg/day. Monitoring the treatment was carried out at 3; 6 and 12 months. Standard one-year comprehensive treatment of patients with UA with comorbid AH resulted in significant improvement of effective endothelial dysfunction in concentric and eccentric left ventricular hypertrophy in 3; 6 and 12 months, however, regression of hypertrophy brachial artery advancing much less mainly in concentric left ventricular hypertrophy. PMID:27089719

  19. Vascular remodeling as compensatory changes in different degrees of varicocele

    Directory of Open Access Journals (Sweden)

    E. S. Severgina

    2013-01-01

    Full Text Available We investigated biosises obtained from children with different varicocele stages and showed the possibility of remodeling development in different type vein walls. Most typical changes were found in the third type vein walls – multiple rolls, composed of muscular and collagen bundles; in the larger first and second type veins markers of arterialization were seen. These processes are the manifestations of adaptive response, which is connected with elevated venous pressure; they can improve testicular hemodynamic.

  20. Vascular remodeling as compensatory changes in different degrees of varicocele

    Directory of Open Access Journals (Sweden)

    E. S. Severgina

    2014-11-01

    Full Text Available We investigated biosises obtained from children with different varicocele stages and showed the possibility of remodeling development in different type vein walls. Most typical changes were found in the third type vein walls – multiple rolls, composed of muscular and collagen bundles; in the larger first and second type veins markers of arterialization were seen. These processes are the manifestations of adaptive response, which is connected with elevated venous pressure; they can improve testicular hemodynamic.

  1. Myocardial Infarction in a Young Female with Palindromic Rheumatism: A Consequence of Negative Remodeling

    Directory of Open Access Journals (Sweden)

    Timothy R. Larsen

    2012-01-01

    Full Text Available Palindromic rheumatism is a rare disease associated with systemic inflammation. Negative or constrictive coronary artery remodeling is typically not seen until the 7th or 8th decade of life. We report a case of a young female with palindromic rheumatism who suffered a non-ST segment elevation myocardial infarction secondary to a flow-limiting lesion that demonstrated negative remodeling by intravascular ultrasound (IVUS.

  2. Die Rolle der Mastzellen im vaskulären Remodelling bei Lungenhochdruck infolge von Linksherzerkrankung

    OpenAIRE

    Hoffmann, Julia

    2012-01-01

    Analyses of functional genomics in PH and associated vascular Remodelling processes identified mast cells as potential targets for novel therapeutic strategies. Mast cells have been implicated in the pathophysiology of lung cancer and asthma but their role in vascular Remodelling and PH remains unclear. Here, we tested the role of mast cells in experimental models of PH owing to left heart disease and pulmonary arterial hypertension using two different approaches. PH with left heart diseas...

  3. mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects

    OpenAIRE

    Goncharova, Elena A

    2013-01-01

    Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, proliferation, and survival that is implicated in various proliferative and metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and cancer. Emerging evidence suggests a potential critical role of mTOR signaling in pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to increased proliferation, resistance to apoptosis, and altered metabolism of cells forming the pulmo...

  4. Long-term internal thoracic artery bypass graft patency and geometry assessed by multidetector computed tomography

    DEFF Research Database (Denmark)

    Zacho, Mette; Lilleoer, Nikolaj Thomas; Kelbaek, Henning;

    2012-01-01

    The left internal thoracic artery (LITA) undergoes vascular remodelling when used for coronary artery bypass grafting. In this study we tested the hypothesis that the extent of the LITA remodelling late after coronary artery bypass grafting assessed by multidetector computed tomography is related...... to the severity of stenosis in the native coronary vessel. One hundred and forty-two patients who had undergone coronary artery bypass grafting including implantation of LITA as conduit to the left anterior descending artery were studied 5 years after surgery. Arterial graft patency and geometry was assessed...

  5. Experimental study on aortic remodeling in sinoaortic denervated rats

    Institute of Scientific and Technical Information of China (English)

    MIAO Chao-yu; TAO Xia; GUAN Yun-feng; YANG You-cai; CHU Zheng-xu; SU Ding-feng

    2001-01-01

    Objective: To study the aortic remodeling produced by chronic sinoaortic denervation (SAD) and its time course, and to study the role of humoral factor in the SAD-induced aortic remodeling. Methods: In rats with chronic SAD or sham operation, the aortic structure was measured by computer-assisted image analysis, the aortic function by isolated artery preparation, and angiotensin Ⅱ concentration by radioimmunoassay. Results and Conclusion: The aortic structural remodeling developed progressively at 4, 8, 16 and 32 weeks after SAD. Aortic structural remodeling after SAD expressed mainly as aortic hypertrophy due to SMC growth and collagen accumulation. The aortic contraction elicited by norepinephrine (NE) was progressively increased 8, 16 and 32 weeks after SAD. The aortic relaxation elicited by acetylcholine (ACh) was depressed 8, 16 and 32 weeks after SAD. In addition, in 32-week SAD rats the NE-induced contraction was not increased by endothelial denudation. These indicated that the increased contraction and depressed relaxation after SAD were related to the change of endothelium and/or the change of interaction between endothelium and SMC. In 10-week SAD rats, plasma angiotensin Ⅱ concentration remained unchanged, whereas aortic angiotensin Ⅱ concentration was significantly increased, suggesting that activation of tissue renin-angiotensin system may be involved in SAD-induced aortic remodeling.

  6. To Remodel or To Build?

    Science.gov (United States)

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  7. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  8. Newer insulin analogues and inhaled insulin

    OpenAIRE

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  9. PARP inhibition and postinfarction myocardial remodeling.

    Science.gov (United States)

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  10. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  11. Сharacteristics of flexible elastic properties of the carotid arteries in women with arterial hypertension

    OpenAIRE

    Коval О.A.; Zubko I.M.

    2013-01-01

    The article presents the results of study of the features of the carotid wall structure using ultrasound scanning with differential measurement of intima and media thickness, as well as characteristics of arterial elasticity in women with hypertension without comorbidities. It is shown that in women with hypertension vascular remodeling occurs mainly in the form of thickening of the intima-media due to increase in the media layer and is associated with remodeling of the left heart. Carotid re...

  12. A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

    Directory of Open Access Journals (Sweden)

    Breno A. A. Falcão

    2015-01-01

    Full Text Available Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH. Coronary vessel remodeling at cross-section (n = 27.639 and lesion (n = 618 levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI, which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

  13. Insulin resistance and exercise tolerance in heart failure patients

    DEFF Research Database (Denmark)

    Snoer, Martin; Monk-Hansen, Tea; Olsen, Rasmus Huan;

    2012-01-01

    Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.......Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage....

  14. 先天性心脏病相关性肺动脉高压肺组织芳香烃受体的表达及其与肺血管重构的相关性研究%The Aryl-hydrocarbon Receptor Expression in Patients of Pulmonary Arterial Hypertension Associated With Congenital Heart Disease and its Relationship to Pulmonary Vascular Remodeling

    Institute of Scientific and Technical Information of China (English)

    罗鹏; 庞玲品; 吴源聪; 陈普文; 朱秀龙; 陈强; 黄石安; 何建国

    2015-01-01

    Objective: To study if there is an aryl-hydrocarbon receptor (AHR) expression in patients of pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) and to explore if the amount of AHR expression related to pulmonary vascular remodeling. Methods:A total of 32 CHD-PAH patients diagnosed by echocardiography and right heart catheterization for surgical repair were enrolled, and the lung tissue biopsy was performed during the operation. The pulmonaryAHR was detected by immunolfuorescence assay, the ratios of vessel wall area/total area (WA/TA) and vessel wall thickness/vessel external diameter (WD/TD) of small pulmonary arteries were calculated with the imaging software, the mRNA expression of AHR, hypoxia-inducible factor-1α (HIF-1α), aryl-hydrocarbon receptor nuclear translocator (ARNT) and vascular endothelial growth factor (VEGF) were examined by RT-PCR. In addition, blood level of AHR was measured by ELISA. Results: There was AHR expression in pulmonary tissue in all 32 patients. And AHR mRNA expressions were positively related to mPAP (r=0.809,P Conclusion: AHR might be involved in pulmonary vascular remodeling in CHD-PAHpatients.%目的:了解先天性心脏病相关性肺动脉高压(CHD-PAH)患者肺组织是否有芳香烃受体(AHR)表达,同时探讨AHR表达量与肺血管重构是否相关。  方法:入选超声心动图和右心导管检查确诊的预行外科修补术的CHD-PAH患者32例。术中行肺组织活检。采用组织免疫荧光检测肺组织标本AHR表达情况,运用图像分析软件计算肺小血管的管壁面积/管总面积(WA/TA)和管壁厚/管外径(WD/TD)2个相对比值,采用实时荧光定量多聚酶链反应(Real-Time PCR)方法检测AHR mRNA、缺氧诱导因子-1α(HIF-1α)mRNA、芳香烃受体核转位蛋白(ARNT)mRNA和血管内皮生长因子(VEGF)mRNA表达情况。此外,术前采集患者外周血,采用酶联免疫吸附法(ELISA

  15. Effect of hemin on the lung development and pulmonary arterial structural remodeling in congenital diaphragmatic hernia: experiment with rats%血晶素对先天性膈疝大鼠模型胎仔肺发育肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    王元祥; 刘文英; 林涵; 徐畅; 唐耘熳; 位永娟; 覃道锐

    2008-01-01

    Objective To assay the effects of prenatal hemin therapy on pulmonary hypoplasia (PH)and pulmonary arterial structural remodeling in congenital diaphragmatic hernia(CDH). Methods Six pregnant female SD rats were randomly divided into 3 equal groups: control group, undergoing gastric perfusion of olive oil once on day 9. 5 and intraperitoneal injection of normal saline on days 11-14: CDH group, undergoing gastric perfusion of nitrofen 125 mg once on day 9. 5 and intraperitoneal injection of normal saline on days 11-14;and hemin group, undergoing gastric perfusion of nitrofen 125 mg once on caesarean section was performed to take out the fetuses to undergo histological examination and image analysis. Results CDH were detected in 28 of the 44(63. 6%)fetuses from the 2 groups receiving nitrofen. The lungs of all CDH group fetuses were hypoplastic, and the fetuses of the hemin group showed improved lung development. The right lung/body weight ratio and pulmonary alveolar area ratio(PAA%)of the hemin group were(16. 6±1. 0)mg/g and(45±6)% respectively, both significantly higher than those of the CDH group[(14. 6±1. 7)mg/g and(28±6)% respectively, P=0. 03 and P<0. 01]. The alveolar septum area ratio(ASA%)of the hemin group was(44±6)%, significantly lower than that of the CDH group[(64±8)%, P<0. 01]. The media thickness percentages(MT%)of pre-acinar artery (PAPA)and intra-acinar artery(IAPA)of the fetuses of the hemin group were(21. 2±2. 2)% and (18. 2±2. 1)% respectively, both significantly lower than those of the CDH group[(24. 3±4. 0)% and (21. 9±3. 9)% respectively, both P<0. 05], which were significantly higher than those of the control group[(20. 0±2. 4)% and(17. 2±2. 3)% respectively, both P<0. 01]. The component ratio of nonmuscularized artery(NMA)in the IAPA level of the hemin group was(78. 2±3. 0)%, significantly higher than that of the CDH group[(72. 8±3. 2)%, P=0. 001]. Conclusion PH and pulmonary arterial structural remodeling are present

  16. Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice.

    Science.gov (United States)

    Tan, Hongmei; Shi, Chengwei; Jiang, Xiaohua; Lavelle, Muriel; Yu, Caijia; Yang, Xiaofeng; Wang, Hong

    2014-01-01

    This study investigated the role and mechanism of Hyperhomocysteinemia (HHcy) on vascular remodeling in mice. We assessed the effect of HHcy on vascular remodeling using a carotid arterial vein patch model in mice with the gene deletion of cystathionine-beta-synthase (Cbs). Vein grafts were harvested 4 weeks after surgery. Cross sections were analyzed using Verhoeff-van Gieson staining, Masson`s Trichrome staining, and immunostaining for morphological analysis and protein level assessment. The effect of Hcy on collagen secretion was examined in cultured rat aortic smooth muscle cells (RASMC). We found that Cbs-/- mice with severe HHcy exhibited thicker neointima and a higher percentage of luminal narrowing in vein grafts. In addition, severe HHcy increased elastin and collagen deposition in the neointima. Further, severe HHcy increases CD45 positive cells and proliferative cells in vein grafts. Finally, Hcy increases collagen secretion in RASMC. These results demonstrate that HHcy increases neointima formation, elastin and collagen deposition following a carotid arterial vein patch. The capacity of Hcy to promote vascular fibrosis and inflammation may contribute to the development of vascular remodeling. PMID:24896329

  17. Glucose-stimulated Cdc42 Signaling Is Essential for the Second Phase of Insulin Secretion*

    OpenAIRE

    Wang, Zhanxiang; Oh, Eunjin; Thurmond, Debbie C.

    2007-01-01

    The small Rho family GTPases Cdc42 and Rac1 have each been shown to function in insulin exocytosis and are presumed to function in actin remodeling and insulin granule mobilization. However, whether either GTPase is required for the mobilization phase of insulin release (second phase) and are linked in a common signaling pathway has remained unknown. Here we demonstrate that small interfering RNA-mediated depletion of Cdc42 from isolated islets results in the selective loss of second-phase in...

  18. Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Rui Zhang; Yunliang Guo

    2006-01-01

    BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family,participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed.OBJ ECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey.DESIGN: A completely randomized grouping design, controlled animal experimentSETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co. Ltd, Wuhan); 12 800 dots chip (Boxing Company,Shanghai).METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created.② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW

  19. The Warburg effect: A new story in pulmonary arterial hypertension.

    Science.gov (United States)

    Peng, Hongyan; Xiao, Yunbin; Deng, Xicheng; Luo, Jingfei; Hong, Chenliang; Qin, Xuping

    2016-10-01

    Pulmonary arterial hypertension (PAH) is a rare yet fatal condition that is characterized by a continuous and notable elevation of pulmonary arterial pressure (PAP), resulting in right heart failure and death. Pulmonary arterial remodelling does not result from abnormal proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) but from pulmonary arterial endothelial cell (PAEC) dysfunction. However, the pathological mechanism of these two types of vascular cells in pulmonary artery remodelling is unclear. The Warburg effect describes aerobic glycolysis wherein cells commonly reprogram their energy metabolism to preferentially utilize glycolysis over oxidative phosphorylation for ATP production. Recent research has demonstrated that the Warburg effect plays a significant role in the development of PAH, which involves the abnormal proliferation of PASMCs and endothelial dysfunction. This review attempts to illustrate the functions of the Warburg effect in PAH, which may provide a new therapeutic target for PAH treatment.

  20. Balloon-assisted coil embolization of a posterior cerebral artery aneurysm via a persistent primitive trigeminal artery: technical note

    Energy Technology Data Exchange (ETDEWEB)

    Schlamann, Marc; Doerfler, Arnd; Forsting, Michael; Wanke, Isabel [University of Essen Medical School, Department of Neuroradiology, Institute of Diagnostic and Interventional Radiology, Essen (Germany); Schoch, Beate [University of Essen Medical School, Department of Neurosurgery, Essen (Germany)

    2006-12-15

    We present a patient with an acutely ruptured, wide-necked aneurysm of the left posterior cerebral artery (PCA) treated with Guglielmi detachable coils using the remodeling technique. Since the left vertebral artery was compressed due to a tumor in the cerebellopontine angle and the right vertebral artery was hypoplastic, we used a carotid artery approach via a persistent primitive trigeminal artery (PPTA) to selectively catheterize the aneurysm. The aneurysm was occluded completely. To our knowledge this is the first case of a wide-necked PCA aneurysm treated via a PPTA and using the remodeling technique. In patients with hypoplastic vertebral arteries and a PPTA, this approach may represent an alternative for selective embolization of posterior circulation aneurysms not amenable to the conventional approach. (orig.)

  1. microRNAs and Cardiovascular Remodeling.

    Science.gov (United States)

    Ono, Koh

    2015-01-01

    Heart failure (HF) is associated with significant morbidity and mortality attributable largely to structural changes in the heart and with associated cardiac dysfunction. Remodeling is defined as alteration of the mass, dimensions, or shape of the heart (termed cardiac or ventricular remodeling) and vessels (vascular remodeling) in response to hemodynamic load and/or cardiovascular injury in association with neurohormonal activation. Remodeling may be described as physiologic or pathologic; alternatively, remodeling may be classified as adaptive or maladaptive. The importance of remodeling as a pathogenic mechanism has been controversial because factors leading to remodeling as well as the remodeling itself may be major determinants of patients' prognosis. The basic mechanisms of cardiovascular remodeling, and especially the roles of microRNAs in HF progression and vascular diseases, will be reviewed here.

  2. Postprandial Vascular Effects of VIAject Compared With Insulin Lispro and Regular Human Insulin in Patients With Type 2 Diabetes

    Science.gov (United States)

    Forst, Thomas; Pfützner, Andreas; Flacke, Frank; Krasner, Alan; Hohberg, Cloth; Tarakci, Eda; Pichotta, Philip; Forst, Senait; Steiner, Solomon

    2010-01-01

    OBJECTIVE Recent studies suggested an impact of prandial insulin delivery on postprandial regulation of tissue blood flow. This study compared the effect of VIAject with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Fourteen patients (seven men; aged 61.5 ± 1.8 years; duration of diabetes 6.6 ± 4.6 years; A1C 7.2 ± 0.5% [mean ± SEM]) received a prandial injection of VIAject, human regular insulin, and insulin lispro. At baseline and after a standardized liquid meal test (Ensure Plus), the postprandial increases in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the postprandial effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured. RESULTS Treatment with VIAject resulted in a significant reduction in the peak postprandial generation of ADMA compared with human insulin and insulin lispro (VIAject −27.3 ± 22.6, human insulin 97.7 ± 24.4, and insulin lispro 66.9 ± 33.9 nmol/l; P < 0.05, respectively). The postprandial increases in nitrotyrosine levels were significantly less after VIAject than after human regular insulin (VIAject −0.22 ± 0.17 vs. human insulin 0.25 ± 0.15 μg/ml; P < 0.05), whereas nitrotyrosine after insulin lispro was in between (insulin lispro 0.09 ± 0.07 μg/ml; NS). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after VIAject compared with those after human insulin or insulin lispro (P < 0.05, respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity. CONCLUSIONS Treatment with VIAject reduced postprandial oxidative stress and improved endothelial function compared with human regular insulin or insulin lispro. PMID:19808913

  3. Myocardial structure, function and ischaemic tolerance in a rodent model of obesity with insulin resistance.

    Science.gov (United States)

    Wensley, I; Salaveria, K; Bulmer, A C; Donner, D G; du Toit, E F

    2013-11-01

    Obesity and its comorbidities (dyslipidaemia, insulin resistance and hypertension) that together constitute the metabolic syndrome are all risk factors for ischaemic heart disease. Although obesity has been reported to be an independent risk factor for congestive heart failure, whether obesity-induced heart failure develops in the absence of increased afterload (induced by hypertension) is not clear. We have previously shown that obesity with insulin resistance decreases myocardial tolerance to ischaemia-reperfusion, but the mechanism for this decreased tolerance remains unclear. We hypothesize that obesity with insulin resistance induces adverse cardiac remodelling and pump dysfunction, as well as adverse changes in myocardial prosurvival reperfusion injury salvage kinase (RISK) pathway signalling to reduce myocardial tolerance to ischaemia-reperfusion. Wistar rats were fed an obesogenic (obese group) or a standard rat chow diet (control group) for 32 weeks. Echocardiography was performed over the 32 weeks before isolated Langendorff-perfused hearts were subjected to 40 min coronary artery ligation followed by reperfusion, and functional recovery (rate-pressure product), infarct size and RISK pathway function were assessed (Western blot analysis). Obesity with insulin resistance increased myocardial lipid accumulation but had no effect on in vivo or ex vivo left ventricular structure/function. Hearts from obese rats had lower reperfusion rate-pressure products (13115 ± 562 beats min(-1) mmHg for obese rats versus 17781 ± 1109 beats min(-1) mmHg for control rats, P < 0.05) and larger infarcts (36.3 ± 5.6% of area at risk in obese rats versus 14.1 ± 2.8% of area at risk in control rats, P < 0.01) compared with control hearts. These changes were associated with reductions in RISK pathway function, with 30-50 and 40-60% reductions in Akt and glycogen synthase kinase 3 beta (GSK-3β) expression and phosphorylation, respectively, in obese rat hearts compared with

  4. Effect of postconditioning on dynamic expression of tenascin-C and left ventricular remodeling after myocardial ischemia and reperfusion

    OpenAIRE

    Taki, Junichi; Inaki, Anri; Wakabayashi, Hiroshi; Matsunari, Ichiro; Imanaka-Yoshida, Kyoko; Ogawa, Kazuma; Hiroe, Michiaki; Shiba, Kazuhiro; Yoshida, Toshimichi; Kinuya, Seigo

    2015-01-01

    Background Tenascin-C (TNC), an extracellular matrix glycoprotein, is expressed transiently in distinct areas in association with active tissue remodeling. This study aimed to explore how ischemic postconditioning (PC) affects myocardial expression of TNC and ventricular remodeling using 125I-labeled anti-TNC antibody (125I-TNC-Ab) in a rat model of ischemia and reperfusion. Methods In control rats (n = 27), the left coronary artery (LCA) was occluded for 30 min followed by reperfusion for 1,...

  5. 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...

  6. Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Rui Zhang; Yunliang Guo

    2006-01-01

    BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family,participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed.OBJ ECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey.DESIGN: A completely randomized grouping design, controlled animal experimentSETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co. Ltd, Wuhan); 12 800 dots chip (Boxing Company,Shanghai).METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created.② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW

  7. Arterial Ageing

    OpenAIRE

    Lee, Seung-Jun; Park, Sung-Ha

    2013-01-01

    Arterial ageing is characterized by age associated degeneration and sclerosis of the media layer of the large arteries. However, besides ageing, clinical conditions, which enhance oxidative stress and inflammation act to accelerate the degree of arterial ageing. In this review, we summarized the pathophysiology and contributing factors that accelerate arterial ageing. Among them, we focused on hypertension, the renin-angiotensin-aldosterone system and vascular inflammation which are modifiabl...

  8. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Disease Organizations (PDF, 293 KB). Alternate Language URL Insulin Resistance and Prediabetes Page Content On this page: ... Nutrition Points to Remember Clinical Trials What is insulin? Insulin is a hormone made in the pancreas, ...

  9. Insulin glargine overdose

    Directory of Open Access Journals (Sweden)

    Fatma Sari Dogan

    2012-01-01

    Full Text Available Insulin glargine is a long acting novel recombinant human insulin analogue indicated to improve glycemic control, in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. The time course of action of insulins including insulin glargine may vary between individuals and/or within the same individual. Insulin glargine is given as a 24-h dosing regimen and has no documented half-life or peak effect. Hypoglycemia is the most common adverse effect of insulin, including insulin glargine. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. We present a case of a 76-year-old male insulin-dependent diabetic patient with refractory hypoglycemia secondary to an intentional overdose of insulin glargine. We would like to highlight the necessity of prolonging IV glucose infusion, for a much longer period than expected from pharmacokinetic properties of these insulin analogues after intentional massive overdose.

  10. New aspects of vascular remodelling: the involvement of all vascular cell types.

    Science.gov (United States)

    McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

    2005-07-01

    Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

  11. Hereditary and environmental influences on arterial function.

    Science.gov (United States)

    Hayward, C S; Benetos, A

    2007-07-01

    1. With the ageing population and increasing heart failure, arterial function has been shown to contribute to cardiovascular risk because of its adverse effects on ventriculovascular coupling. Population studies have confirmed independent prognostic information of arterial stiffening on cardiovascular survival. 2. The term 'arterial function' encompasses a range of phenotypes, including measures of arterial structure/remodelling, measures of arterial wall mechanics, surrogate measures of stiffness and of wave reflection. There exists significant interaction between these measures and none is truly independent of the others. Added to this complexity is the recognition that, although arterial function has a strong genetic component, quantification requires a range of techniques from twin to family and population studies. 3. The contribution of heritability is often derived from statistical models with input from genomic scanning and candidate gene studies. Studies to date confirm a significant heritable component for the majority of phenotypes examined. However, it has also been recognized that the factors involved in blood pressure maintenance are likely to be separate to those in arterial structural degeneration with ageing. Candidate genes for arterial function go beyond those of the sympathetic and renin-angiotensin systems and include genes involved in signalling pathways and extracellular matrix modulation. 4. The present review examines the evidence for heritability of the major arterial function phenotypes with environmental and ageing modulation. A brief overview of the impact of atherosclerotic risk factors on arterial function is included.

  12. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow

    OpenAIRE

    Vodstrcil, Lenka A.; Tare, Marianne; Novak, Jacqueline; Dragomir, Nicoleta; Ramirez, Rolando J.; Wlodek, Mary E.; Conrad, Kirk P.; Parry, Laura J.

    2012-01-01

    Normal pregnancy involves dramatic remodeling of the uterine vasculature, with abnormal vascular adaptations contributing to pregnancy diseases such as preeclampsia. The peptide hormone relaxin is important for the renal and systemic hemodynamic adaptations to pregnancy, and has been shown to increase arterial compliance and outward hypertrophic remodeling. Therefore, we investigated the possibility that relaxin acts on its receptor, RXFP1, to mediate uterine artery compliance in late pregnan...

  13. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  14. A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

    DEFF Research Database (Denmark)

    Olsen, M H; Andersen, U B; Wachtell, K;

    2000-01-01

    We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension....

  15. Effects of dynamicly adjusting insulin pump intake to control blood glucose after coronary artery bypass grafting%动态调节胰岛素泵入量在冠状动脉旁路移植术后血糖控制的效果评价

    Institute of Scientific and Technical Information of China (English)

    李娜; 生伟; 尹红

    2015-01-01

    ObjectiveTo discuss the effects of dynamicly adjusting insulin pump intake to control blood glucose after coronary artery bypass grafting(CABG).Methods A total of 121 patients undergoing coronary artery bypass surgery between October 2013 and October 2013 were divided into observation group(n=65)and control group (n=56). Insulin(40U Insulin+20mL normal saline )was infused by micro-pump in observation group,The amount of insulin was increased by 2U/h-4U/h before the meal,the insulin pump dose after two hours was adjusted according to the results of blood glucose.Insulin was infused by micro-pump according to the results of blood glucose in control group.Then the therapeutic effects of the two groups were assessed.Results There was no hypoglycemia occurred in the observation group and 5 cases in the control group,the difference was statistically significant(P<0.05).The blood glucose fluctuation was small and there was no wound infection,but there were 4 cases of wound infection in the control group, the difference was statistically significant(P<0.05).Conclusion Dynamic regulation of insulin pump in the amount of blood glucose control method,can effectively control blood glucose in the range of stability,reduce the incidence of complications after CABG operation,improve surgical treatment effect, and promote the rehabilitation of patients.%目的:探讨冠状动脉旁路移植术(CABG)后动态调节胰岛素泵入量控制血糖的效果。方法2013年10月~2014年10月选取就诊于青岛市市立医院心外科选择CABG的患者121例,随机分为观察组(65例)和对照组(56例),观察组术后给予微量泵持续注射普通胰岛素(40U胰岛素+20mL生理盐水),在患者进食前将胰岛素泵入量调高2~4U/h,在进食2h后,根据血糖结果再调整胰岛素泵入量。对照组根据血糖监测结果调整胰岛素泵入量,比较两组治疗效果。结果观察组术后无低血糖发生,对照组5例,

  16. The relationship between amount of cigarette smoked and insulin resistance in male patients with coronary artery disease%男性冠心病患者吸烟量与胰岛素抵抗的关系

    Institute of Scientific and Technical Information of China (English)

    范小明; 吕安康; 沈卫峰; 马晓晔; 吴祁红; 张瑞岩

    2011-01-01

    Objective To investigate the relationship between smoking and insulin resistance in non-obese male patients with CAD. Methods 414 consecutive non-obese male patients with angiographically-documented CAD(luminal diameter narrowing>50%)were recruited,including 113 nonsmokers and 301 smokers.With 99 miht smokers(<400 packs/year),95 medium smokers(400-799 packs/year)and 107 heavy smokers(≥800 packs/year).Insulin resistance index(IRI)was expressed by homeostasis model assessment for insulin resistance(HOMA-IR)calculated by the formula of[fasting serum glucose(mmol/L)×fasting plasma insulin(mU/L)]/22.5.IRI≥2.69 was defined as insulin resistance,while IRI<2.69 was insulin sensitive.Fasting glucose,fasting insulin and IRI were recorded and odds ratio for the incidence of insulin resistance was calculated.Results Fasting glucose was higher in heavy smokers (5.86 mmol/L)than that in nonsmokers(5.51 mmol/L,P=0.037)and mild smokers(5.33 mmol/L,P=0.014).Fasting insulin and IRI were also significantly higher in heavy smokers(10.25 mU/L)than those in non-smokers(8.72 mU/L,P=0.0231,respectively)and mild smokers(8.67 mU/L,P=0.023 1).Compared with nonsmokers,the odds ratio for the incidence of insulin resistance was 1.53(95%CI 0.55-2.94;P=0.027)in medium smokers and 1.89(95%CI 0.49-3.14;P=0.018)in heavy smokers.Conclusions The relationship between smoking and insulin resistance is highly dose dependent in non-obese male patients with CAD.%目的 探讨非肥胖男性冠心病患者胰岛素抵抗与吸烟总量的关系.方法 连续性非肥胖的冠心病患者共414例,分为从不吸烟组(113例)和吸烟组(301例).通过空腹m糖、空腹胰岛素和胰岛素抵抗指数,分析其与吸烟量关系.结果 与不吸烟者相比,胰岛素抵抗发生风险OR值在吸烟总量<400支/年吸烟者中为1.09,400~799支/年吸烟者为1.53,≥800支/年吸烟者为1.89.结论 在非肥胖的男性冠心病患者中,胰岛素抵抗的发生风险与吸烟总量呈剂量依赖关系.

  17. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik;

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  18. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications.

  19. Association among circulating endothelial progenitor cells, insulin resistance and severity of coronary lesions in patients with coronary artery disease%冠心病患者胰岛素水平与内皮祖细胞及冠状动脉病变的相关性

    Institute of Scientific and Technical Information of China (English)

    钱德慧; 黄岚; 赵晓辉; 周音频; 崔斌; 宋耀明; 李爱民; 付晓岚

    2008-01-01

    目的 探讨冠心病患者不同胰岛素水平与循环内皮祖细胞(EPC)数量、功能及冠状动脉病变程度的关系并探讨相关临床意义.方法 69例经选择性冠状动脉造影证实的冠心病患者,按胰岛素水平高低分为胰岛素抵抗(IR)组和胰岛素敏感(IS)组,另设25例健康对照者.采集研究对象外周血以激酶插入区域受体(KDR)和CD133双阳性为循环EPC标记行流式细胞分析,同时采血进行EPC的分离培养,7 d后鉴定并检测增殖及迁移能力,将各组的一般临床资料,循环EPC数量、迁移、增殖能力指标、稳态模型胰岛素抵抗指数(HOMA-IR)及冠状动脉病变Gensini评分进行统计学分析.结果 IR组循环EPC数量明显少于IS组[(0.34±0.08)‰比(0.47±0.09)‰,P<0.01],HOMA-IR自然对数与循环EPC数量呈负相关(r=-0.291,P=0.01),循环EPC数量与Gensini评分呈负相关(r=-0.3984,P=0.006).IR组的增殖能力和迁移能力均低于IS组减弱(P<0.05).结论 冠心病患者血清胰岛素水平与循环EPC数量呈负相关.循环EPC数量及功能与冠状动脉病变程度呈负相关;IR或高胰岛素血症可能部分通过损害循环EPC的数量及功能,从而影响冠状动脉病变程度.%Objective To investigate the correlation between the number and activity of circulating endothelial progenitor cells (EPCs), insulin resistance and severity of coronary lesions in patients with coronary artery disease (CAD). Methods Patients with coronary angiography evidenced CAD were divided in insulin resistance group ( IR, n = 25 ) and insulin sensitive group ( IS, n = 44) according to insulin level, 25 health volunteers served as control. Circulating EPCs were marked as KDR/CD133<'+ cells via fluorescence- activated cell sorter analysis. EPCs were also isolated from peripheral blood and cultured in vitro for 7 days, identified by DiI-acLDL uptake and lectin staining methods. EPCs migration activities were determined by modified Boyden chamber assay

  20. Cardiac Remodeling After Atrial Fibrillation Ablation

    Directory of Open Access Journals (Sweden)

    Li-Wei Lo, MD; Shih-Ann Chen, MD

    2013-06-01

    Full Text Available Radiofrequency catheter ablation procedures are considered a reasonable option for patients with symptomatic, drug refractory atrial fibrillation (AF. Ablation procedures have been reported to effectively restore sinus rhythm and provide long-term relief of symptoms. Both electrical and structural remodeling occurs with AF. A reversal of the electrical remodeling develops within 1 week after restoration to sinus rhythm following the catheter ablation. The recovery rate is faster in the right atrium than the left atrium. Reverse structural remodeling takes longer and is still present 2 to 4 months after restoration of sinus rhythm. The left atrial transport function also improves after successful catheter ablation of AF. Left atrial strain surveys from echocardiography are able to identify patients who respond to catheter ablation with significant reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic resonance imaging is also able to determine the degree of atrial fibrosis and is another tool to predict the reverse remodeling after ablation. The remodeling process is complex if recurrence develops after ablation. Recent evidence shows that a combined reverse electrical and structural remodeling occurs after ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical remodeling without any structural remodeling develops in those with recurrence involving chronic AF. Whether progressive atrial remodeling is the cause or consequence during the recurrence of AF remains obscure and requires further study.

  1. Insulin Resistance and Hyperinsulinemia

    OpenAIRE

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  2. Autoantibodies against human insulin.

    OpenAIRE

    Wilkin, T J; Nicholson, S.

    1984-01-01

    Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only hum...

  3. NEWER STRATEGIES FOR INSULIN DELIVERY

    OpenAIRE

    Singh Nisha; Lokwani Priyanka; Kaushik Avinash Yogendraji; Sharma Ritu

    2011-01-01

    Insulin is a proteinaceous hormone produced in the islets of Langerhans in the pancreas and used as a treatment in the diabetes mellitus. Successful oral insulin delivery involves overcoming the enzymatic and physical barriers and taking steps to conserve bioactivity during formulation processing. Newer strategies for insulin delivery include insulin pen injector, Refillable insulin injection pen, Insulin Syringe, Transfersome and Implantable insulin pumps.

  4. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  5. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  6. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  7. Vascular Stiffness in Insulin Resistance and Obesity

    Directory of Open Access Journals (Sweden)

    Guanghong eJia

    2015-08-01

    Full Text Available Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

  8. Gender differences in cardiac hypertrophic remodeling.

    Science.gov (United States)

    Patrizio, Mario; Marano, Giuseppe

    2016-01-01

    Cardiac remodeling is a complex process that occurs in response to different types of cardiac injury such as ischemia and hypertension, and that involves cardiomyocytes, fibroblasts, vascular smooth muscle cells, vascular endothelial cells, and inflammatory cells. The end result is cardiomyocyte hypertrophy, fibrosis, inflammation, vascular, and electrophysiological remodeling. This paper reviews a large number of studies on the influence of gender on pathological cardiac remodeling and shows how sex differences result in different clinical outcomes and therapeutic responses, with males which generally develop greater cardiac remodeling responses than females. Although estrogens appear to have an important role in attenuating adverse cardiac remodeling, the mechanisms through which gender modulates myocardial remodeling remain to be identified. PMID:27364397

  9. Insulin pumps.

    Science.gov (United States)

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing to see more research on the psychosocial aspects of CSII during the year, both from the point of view of how psychological beliefs influence outcomes on CSII (is there a type of patient who does particularly well or poorly on CSII?) and how CSII affects psychological factors like mood, behaviour and quality of life. Quality of

  10. Diabetes Mellitus, ArterialWall, and Cardiovascular Risk Assessment

    OpenAIRE

    Michaela Kozakova; Carlo Palombo

    2016-01-01

    Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structura...

  11. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  12. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    OpenAIRE

    RobertRoot-Bernstein

    2014-01-01

    Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance. Objectives: To determine the binding constants of steroid hormones to insulin, the insulin recepto...

  13. Pressão arterial, respostas metabólicas e autonômicas à insulina e infusão de intralipid® em pacientes chagásicos Presión arterial, respuestas metabólicas y autonómicas a la insulina e infusión de intralipid® en pacientes chagásicos Blood pressure, metabolic and autonomic responses to insulin and intralipid® infusion in chagasic patients

    Directory of Open Access Journals (Sweden)

    Claudia Cristina Soares Silva

    2012-03-01

    con la forma indefinida de la Enfermedad de Chagas y 12 voluntarios sanos. RESULTADOS: La presión arterial basal y la frecuencia cardíaca fueron similares en los dos grupos. Los niveles plasmáticos de noradrenalina estaban ligeramente más elevados en el grupo de pacientes chagásicos. Después del Test de Tolerancia a la Insulina (TTI, se produjo una ostensible disminución en la glucosa de los dos grupos. La Infusión de ILH trajo como consecuencia el aumento de la presión arterial en ambos grupos, pero no hubo ningún cambio significativo en la noradrenalina plasmática. El componente de Baja Frecuencia (BF, fue similar y aumentó de forma parecida en ambos grupos. El componente de Alta Frecuencia (AF se presentó con un menor nivel en el grupo chagásico. CONCLUSIONES: Los pacientes con una forma indeterminada de la Enfermedad de Chagas, presentaron un aumento en la actividad simpática al momento basal y una respuesta inadecuada a la insulina. También tuvieron un menor componente de alta frecuencia y de sensibilidad barorrefleja, que fue perjudicado en el momento basal y durante la infusión de intralipid® y heparina.BACKGROUND: Intralipid and heparin infusion results in increased blood pressure and autonomic abnormalities in normal and hypertensive individuals. OBJECTIVE: To evaluate insulin sensitivity and the impact of Intralipid and heparin (ILH infusion on hemodynamic, metabolic, and autonomic response in patients with the indeterminate form of Chagas' disease. METHODS: Twelve patients with the indeterminate form of Chagas' disease and 12 healthy volunteers were evaluated. RESULTS: Baseline blood pressure and heart rate were similar in both groups. Plasma noradrenaline levels were slightly increased in the Chagas' group. After insulin tolerance testing (ITT, a significant decline was noted in glucose in both groups. ILH infusion resulted in increased blood pressure in both groups, but there was no significant change in plasma noradrenaline. The low

  14. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  15. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T;

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  16. Exercise and arterial adaptation in humans: uncoupling localized and systemic effects

    NARCIS (Netherlands)

    Rowley, N.J.; Dawson, E.A.; Birk, G.K.; Cable, N.T.; George, K.; Whyte, G.; Thijssen, D.H.J.; Green, D.J.

    2011-01-01

    Previous studies have established effects of exercise training on arterial wall thickness, remodeling, and function in humans, but the extent to which these changes are locally or systemically mediated is unclear. We examined the brachial arteries of the dominant (D) and nondominant (ND) upper limbs

  17. Generalised insulin oedema after intensification of treatment with insulin analogues

    OpenAIRE

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  18. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    Science.gov (United States)

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli. PMID:12769691

  19. Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes

    OpenAIRE

    Li, Weiguo; Kelly-Cobbs, Aisha I.; Mezzetti, Erin M.; Fagan, Susan C; Ergul, Adviye

    2010-01-01

    Diabetes increases the risk as well as the poor outcome of stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media:lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeli...

  20. Molecular Mechanisms of Insulin Resistance Development

    Directory of Open Access Journals (Sweden)

    Vsevolod Arsen'evich Tkachuk

    2014-05-01

    Full Text Available Insulin resistance (IR is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell. Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

  1. I-123-insulin: A new marker for hepatoma

    Energy Technology Data Exchange (ETDEWEB)

    Sodoyez, J.C.; Goffaux, F.S.; Fallais, C.; Bourgeois, P.

    1984-01-01

    Previous studies have demonstrated that carrier-free I-123-Tyr Al4 insulin was taken up by the liver (by a saturable mechanism) and by the kidneys (by a non saturable mechanism). Autoradiographs of rat liver after injection of I-125-insulin showed that binding specifically occurred at the plasma membrane of the hepatocytes. I-123-Insulin binding to the hepatocyte plasma membrane appeared mediated by specific receptors. Indeed it was blocked by antibodies to the insulin receptors and by an excess of native insulin. Futhermore insulin derivatives with low biological potency (proinsulin and desoctapeptide insulin) did not inhibit I-123-insulin binding to the hepatocytes. I-123-Insulin (1.3 mCi) was I.V. injected into a patient in whom the right liver lobe was normal (normal uptake of Tc-99m-colloid sulfur) but the left liver lobe was occupied by a voluminous hepatoma (no uptake of Tc-99m-colloid sulfur). Liver blood supply was also studied by Tc-99m-pyrophosphate-labeled red cells. Computer analysis of the data revealed that compared to the normal liver lobe, binding of I-123-insulin to the hepatoma was more precocious (vascularization through the hepatic artery and not the portal vein), more intense and more prolonged (half-lives were 6 min in the normal liver and 14 min in the hepatoma). These results are consistent with characteristics of hepatoma cells in culture in which high insulin binding capacity contrasts with a markedly decreased insulin degrading activity. It is concluded that I-123-insulin may be used as a specific marker of hepatoma in man.

  2. I-123-insulin: A new marker for hepatoma

    International Nuclear Information System (INIS)

    Previous studies have demonstrated that carrier-free I-123-Tyr Al4 insulin was taken up by the liver (by a saturable mechanism) and by the kidneys (by a non saturable mechanism). Autoradiographs of rat liver after injection of I-125-insulin showed that binding specifically occurred at the plasma membrane of the hepatocytes. I-123-Insulin binding to the hepatocyte plasma membrane appeared mediated by specific receptors. Indeed it was blocked by antibodies to the insulin receptors and by an excess of native insulin. Futhermore insulin derivatives with low biological potency (proinsulin and desoctapeptide insulin) did not inhibit I-123-insulin binding to the hepatocytes. I-123-Insulin (1.3 mCi) was I.V. injected into a patient in whom the right liver lobe was normal (normal uptake of Tc-99m-colloid sulfur) but the left liver lobe was occupied by a voluminous hepatoma (no uptake of Tc-99m-colloid sulfur). Liver blood supply was also studied by Tc-99m-pyrophosphate-labeled red cells. Computer analysis of the data revealed that compared to the normal liver lobe, binding of I-123-insulin to the hepatoma was more precocious (vascularization through the hepatic artery and not the portal vein), more intense and more prolonged (half-lives were 6 min in the normal liver and 14 min in the hepatoma). These results are consistent with characteristics of hepatoma cells in culture in which high insulin binding capacity contrasts with a markedly decreased insulin degrading activity. It is concluded that I-123-insulin may be used as a specific marker of hepatoma in man

  3. Endovascular treatment of wide-necked intracranial aneurysms using of "remodeling technique" with the HyperForm balloon

    Institute of Scientific and Technical Information of China (English)

    MU Shi-qing; YANG Xin-jian; LI You-xiang; ZHANG You-ping; L(U) Ming; WU Zhong-xue

    2008-01-01

    Background Aneurysms with wide-necked or a large neck/fundus ratio, especially located on an arterial bifurcation or a small artery, are challenges for interventional neuroradiologist because of the risk of coil migration or coil protrusion into the parent vessels. Our study was designed to improve the efficacy and safety of the "remodeling technique" with the HyperForm balloon for these difficult aneurysms and was confirmed by a follow-up result. Methods From June 2004 to September 2006, forty-two patients(20 men, 22 women)with wide-necked or large neck/fundus ratio aneurysms were treated by using the"remodeling technique"with the HyperForm balloon. Results Forty wide-necked aneurysms were successfully treated with the HyperForm balloon remodeling technique with only two failed cases. Final results consisted of total occlusion in 34 cases(80.9%), subtotal in 4 (9.5%) and incomplete in 2(4.8%). One aneurysmal rupture occurred, but no clinical consequence was shown. No thromboembolic events were observed during treatment. Final angiographic follow-up time ranged from 3 to 18 months. Conclusions The "remodeling technique" with the HyperForm balloon is a very useful tool in the treatment of wide-necked or unfavorable neck/fundus ratio intracranial aneurysms-located on an arterial bifurcation or a small artery and, especially, located on the bifurcation of a large artery and a small one. In our experience, this technique provided a safe and efficient treatment for difficult aneurysms when the standard remodeling technique might have failed.

  4. Multiscale Simulation of Protein Mediated Membrane Remodeling

    OpenAIRE

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    Proteins interacting with membranes can result in substantial membrane deformations and curvatures. This effect is known in its broadest terms as membrane remodeling. This review article will survey current multiscale simulation methodologies that have been employed to examine protein-mediated membrane remodeling.

  5. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  6. Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

    DEFF Research Database (Denmark)

    Blædel, Martin Mads; Boonen, Harrie C.M.; Sams Nielsen, Anette;

    isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined....... Arteries that had been incubated in the presence of either D-glucose, insulin, or TNFa alone, displayed unchanged sensitivity and max. responses to NA as compared to control conditions (21 hour incubation in EBM-2 only). However, when arteries were incubated in combinations of glucose, insulin or TNF...

  7. Giving an insulin injection

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000660.htm Giving an insulin injection To use the sharing features on this ... and syringes. Filling the Syringe - One Type of Insulin Wash your hands with soap and water. Dry ...

  8. Insulin Lispro Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... sweating weakness muscle cramps abnormal heartbeat shortness of breath large weight gain in a short period of ...

  9. Nucleosome dynamics during chromatin remodeling in vivo.

    Science.gov (United States)

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  10. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  11. The Insulin Pump

    OpenAIRE

    Toews, C. J.

    1985-01-01

    Subcutaneous continuous insulin infusion systems deliver insulin at a basal rate designed to keep blood glucose levels normal in the non-fed state. Additional insulin is delivered at meal time. Pumps can provide near optimal control of blood glucose concentrations in selected, highly motivated patients. The pump provides better diabetic control than once daily insulin injections, although several daily injections can provide comparable control. Optimal control with the pump causes some short-...

  12. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingol

  13. Remodelling of choroidal blood flow in radiation choroidopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko [Gunma Univ., Maebashi (Japan). School of Medicine

    1997-02-01

    Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

  14. Energetic and spatial constraints of arterial networks

    Directory of Open Access Journals (Sweden)

    Sandro Rossitti

    1995-06-01

    Full Text Available The principle of minimum work (PMW is a parametric optimization model for the growth and adaptation of arterial trees. A balance between energy dissipation due to frictional resistance of laminar flow (shear stress and the minimum volume of the blood and vessel wall tissue is achieved when the vessel radii are adjusted to the cube root of the volumetric flow. The PMW is known to apply over several magnitudes of vessel calibers, and in many different organs, including the brain, in humans and in animals. Animal studies suggest that blood flow in arteries is approximately proportional to the cube of the vessel radius, and that arteries alter their caliber in response to sustained changes of blood flow according to PMW. Remodelling of the retinal arteriolar network to long-term changes in blood flow was observed in humans. Remodelling of whole arterial networks occurs in the form of increase or diminishing of vessel calibers. Shear stress induced endothelial mediation seems to be the regulating mechanism for the maintenance of this optimum blood flow/vessel diameter relation. Arterial trees are also expected to be nearly space filing. The vascular system is constructed in such a way that, while blood vessels occupy only a small percentage of the body volume leaving the bulk to tissue, they also crisscross organs so tightly that every point in the tissue lies on the boundary between an artery and a vein. This review describes how the energetic optimum principle for least energy cost for blood flow is also compatible with the spatial constraints of arterial networks according to concepts derived from fractal geometry.

  15. Remodeling in the ischemic heart: the stepwise progression for heart

    Directory of Open Access Journals (Sweden)

    J.G. Mill

    2011-09-01

    Full Text Available Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI has decreased in the last decades. However, the incidence of heart failure (HF in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

  16. Analysis of Arterial Mechanics During Head-Down-Tilt Bed Rest

    Science.gov (United States)

    Elliott, Morgan B.; Martin, David S.; Westby, Christian M.; Stenger, Michael B.; Platts, Steven H.

    2014-01-01

    Carotid, brachial, and tibial arteries reacted differently to HDTBR. Previous studies have not analyzed the mechanical properties of the human brachial or anterior tibial arteries. After slight variations during bed-rest, arterial mechanical properties and IMT returned to pre-bed rest values, with the exception of tibial stiffness and PSE, which continued to be reduced post-bed rest while the DC remained elevated. The tibial artery remodeling was probably due to decreased pressure and volume. Resulting implications for longer duration spaceflight are unclear. Arterial health may be affected by microgravity, as shown by increased thoracic aorta stiffness in other ground based simulations (Aubert).

  17. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan;

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  18. Insulin enhances glucose-stimulated insulin secretion in healthy humans

    OpenAIRE

    Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; O'Shea, Sheila; Stefanovski, Darko; Bergman, Richard N.; Rogatsky, Eduard; Stein, Daniel T.; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.

    2010-01-01

    Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) c...

  19. Carotid artery surgery

    Science.gov (United States)

    Carotid endarterectomy; CAS surgery; Carotid artery stenosis - surgery; Endarterectomy - carotid artery ... through the catheter around the blocked area during surgery. Your carotid artery is opened. The surgeon removes ...

  20. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  1. Deficiency of Nox2 prevents angiotensin II-induced inward remodeling in cerebral arterioles

    Directory of Open Access Journals (Sweden)

    Siu-Lung eChan

    2013-06-01

    Full Text Available Angiotensin II is an important determinant of inward remodeling in cerebral arterioles. Many of the vascular effects of angiotensin II are mediated by reactive oxygen species generated from homologues of NADPH oxidase with Nox2 predominating in small arteries and arterioles. Therefore, we tested the hypothesis that superoxide generated by Nox2 plays a role in angiotensin II-induced cerebral arteriolar remodeling. We examined Nox2-deficient and wild-type mice in which a pressor or a non-pressor dose of angiotensin II (1000 or 200 ng/kg/day or saline was infused for 4 weeks via osmotic minipumps. Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of cerebral arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area (by histology and superoxide level (by hydroethidine staining of cerebral arterioles were determined ex vivo. The pressor, but not the non-pressor, dose of angiotensin II significantly increased systolic arterial pressure in both wild-type and Nox2-deficient mice. Both doses of angiotensin II increased superoxide levels and significantly reduced external diameter in maximally dilated cerebral arterioles in wild-type mice. Increased superoxide and inward remodeling were prevented in Nox2-deficient mice. Moreover, only the pressor dose of AngII increased cross-sectional area of arteriolar wall in wild-type mice and was prevented in Nox2-deficient mice. In conclusion, superoxide derived from Nox2-containing NADPH oxidase plays an important role in angiotensin II-mediated inward remodeling in cerebral arterioles. This effect appears to be independent of pressure and different from that of hypertrophy.

  2. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  3. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  4. Evaluation of left ventricular remodelling in patients with chronic ischemic heart disease using multislice computer tomography and magnetic resonance tomography

    International Nuclear Information System (INIS)

    The article presents the results of MSCT and MRI of the heart in 57 patients with chronic coronary heart disease. It determined the relationship between structural and functional changes in the left ventricle and the degree of left coronary artery stenosis. Also determined were the link between the ischemic left ventricular remodeling and depth of myocardial damage in patients with coronary heart disease and postinfarction cardiosclerosis. MSCT and MRI are highly reliable imaging technique used to evaluate the infarcted and viable myocardium and post infarct cardiac remodeling process

  5. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    OpenAIRE

    Zhipeng Zeng; Kunwu Yu; Long Chen; Weihua Li; Hong Xiao; Zhengrong Huang

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significant...

  6. Prognostic heterogeneity of diastolic abnormalities along left ventricular remodeling continuum according to survival rates and laser polarimetry of blood

    Science.gov (United States)

    Boychuk, T. M.; Ivashchuk, O. I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Y.

    2012-01-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  7. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-07-01

    Full Text Available Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance.Objectives: To determine the binding constants of steroid hormones to insulin, the insulin receptor, and insulin-like peptides derived from the insulin receptor; and to investigate the effect of estrogens on the binding of insulin to its receptor.Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  8. Carotid Artery Screening

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Carotid Artery Screening What is carotid artery screening? Who should consider ... about carotid artery screening? What is carotid artery screening? Screening examinations are tests performed to find disease ...

  9. Insulinorresistencia y su relación con medidas antropométricas y presión arterial en un grupo de empleados hospitalarios, aparentemente sanos Insulin resistance and its relation to anthropometric measurements and blood pressure in a group of apparently healthy hospital employees

    Directory of Open Access Journals (Sweden)

    G.A Bonneau

    2011-03-01

    Full Text Available La resistencia insulínica es una disminución de la función biológica de la insulina caracterizada por requerir un alto nivel de insulina plasmática para mantener la homeostasis metabólica. Su presencia está asociada con mayor riesgo de enfermedad cardiovascular. Nos propusimos conocer la frecuencia de hiperinsulinemia e insulinorresistencia en empleados del hospital Dr. Ramón Madariaga, correlacionar la insulinorresistencia a través del índice HOMA con edad, presión arterial, obesidad y obesidad abdominal y evaluar su relación con sexo, presión arterial, obesidad y obesidad abdominal. Se estudiaron 170 sujetos de ambos sexos que tenían entre 27 y 74 años de edad, de los cuales 134 fueron de sexo femenino y 36 de sexo masculino. Se obtuvieron datos antropométricos y presión arterial. Se realizó una extracción sanguínea con un ayuno de 12 horas para las determinaciones bioquímicas. Todos los análisis estadísticos se realizaron utilizando el programa Epi-info 2000, con un nivel de confianza del 95 % y un nivel de significación According to 2008 data from the Ministry of Public Health of the Province of Misiones, cardiovascular disease is the main cause of mortality in that province, with a proportional mortality ratio of 28.3 %, and with a process known as arteriosclerosis as the main responsible factor. Arteriosclerosis is a chronic inflammatory process where endothelial dysfunction plays a major role. Insulin resistance (IR, described as a condition in which there is a decrease in the biological function of insulin and high plasma levels of insulin are required to maintain metabolic homeostasis, promotes atherosclerotic development and its presence is associated with an increased risk of cardiovascular disease. Our aim was to determine the frequency of hyperinsulinemia and IR in a group of employees at the Public Provincial Hospital Dr. Ramón Madariaga, to correlate IR with age, blood pressure, general and abdominal

  10. Insulin analogs and cancer

    Directory of Open Access Journals (Sweden)

    Laura eSciacca

    2012-02-01

    Full Text Available Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R, prevalent activation of the ERK rather than the AKT intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to IR but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin

  11. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  12. Concentrated insulins: the new basal insulins

    OpenAIRE

    Lamos EM; Younk LM; Davis SN

    2016-01-01

    Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with in...

  13. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  14. Raise the Floor When Remodeling Science Labs

    Science.gov (United States)

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  15. Transforming Growth Factor-β1 Induces Transdifferentiation of Fibroblasts into Myofibroblasts in Hypoxic Pulmonary Vascular Remodeling

    Institute of Scientific and Technical Information of China (English)

    Yong-Liang JIANG; Ai-Guo DAI; Qi-Fang LI; Rui-Cheng HU

    2006-01-01

    The muscularization of non-muscular pulmonary arterioles is animportant pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-β 1 (TGF-β 1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles. It was found that mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. The distribution of nonmuscular, partially muscular, and muscular vessels was significantly different after 7 d of hypoxia. Immunocytochemistry results demonstrated that the expression of α-smooth muscle actin was increased in intra-acinar pulmonary arteries with increasing hypoxic time. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was poorly positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia. The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum. Taken together, our results suggested that TGF-β1 induces transdifferentiation of fibroblasts into myofibroblasts, which is important in hypoxic pulmonary vascular remodeling.

  16. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    OpenAIRE

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu; Cao, Wenhong

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative s...

  17. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.

    OpenAIRE

    RADERMECKER, Régis; Scheen, André

    2007-01-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenic...

  18. Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.

    Science.gov (United States)

    Facchini, F S; DoNascimento, C; Reaven, G M; Yip, J W; Ni, X P; Humphreys, M H

    1999-04-01

    The objective of this study was to investigate the relationships among various humoral factors thought to be involved in the regulation of blood pressure during high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin resistance was assessed by the steady-state plasma glucose concentration at the end of a 3-hour insulin suppression test. Insulin resistance correlated inversely with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The increase in mean arterial pressure associated with the high-sodium diet correlated directly with the gain in weight (P<0.05) and inversely with the increase in urinary nitrate excretion (P<0.0001). In a multiple regression model, more than 2/3 of the variance in mean arterial pressure was accounted for by the gain in weight and change in urinary nitrate excretion. The steady-state plasma glucose concentrations obtained with the 2 diets were similar, indicating that insulin resistance was unaffected by sodium intake. During high sodium intake, plasma renin activity and aldosterone decreased and plasma atrial natriuretic peptide increased; these changes did not correlate with the change in mean arterial pressure, insulin resistance, or change in urinary nitrate excretion. To the extent that urinary nitrate excretion reflects activity of the endogenous nitric oxide system, these results suggest that the salt sensitivity of mean arterial pressure may be related to blunted generation of endogenous nitric oxide. The results also demonstrate that insulin-resistant individuals have an impaired natriuretic response to high sodium intake. PMID:10205239

  19. Chromatin Modification and Remodeling in Heart Development

    Directory of Open Access Journals (Sweden)

    Paul Delgado-Olguín

    2006-01-01

    Full Text Available In organogenesis, cell types are specified from determined precursors as morphogenetic patterning takes place. These events are largely controlled by tissue-specific transcription factors. These transcription factors must function within the context of chromatin to activate or repress target genes. Recent evidence suggests that chromatin-remodeling and -modifying factors may have tissue-specific function. Here we review the potential roles for chromatin-remodeling and -modifying proteins in the development of the mammalian heart.

  20. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  1. Diagnostic tools assessing airway remodelling in asthma.

    Science.gov (United States)

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. PMID:22236733

  2. Immune Mechanisms in Arterial Hypertension.

    Science.gov (United States)

    Wenzel, Ulrich; Turner, Jan Eric; Krebs, Christian; Kurts, Christian; Harrison, David G; Ehmke, Heimo

    2016-03-01

    Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

  3. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  4. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so......-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

  5. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T;

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  6. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin;

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  7. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling

    OpenAIRE

    Broide, David H.

    2008-01-01

    Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be due to persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodel...

  8. A Semi-Automated Quantification of Pulmonary Artery Dimensions in Computed Tomography Angiography Images

    OpenAIRE

    Berty, Holly L.; Simon, Marc; Chapman, Brian E.

    2012-01-01

    Quantifying vascular dimensions may provide a non-invasive means of diagnosing a variety of vascular diseases, including pulmonary hypertension, a progressive, potentially fatal disease that results in the remodeling of the pulmonary vasculature. Currently the gold standard for diagnosis of pulmonary hypertension is through right heart catheterization, an invasive and costly procedure. Since pulmonary hypertension is associated with the remodeling of the pulmonary arteries, quantifying vascul...

  9. Etiopathogenesis of insulin autoimmunity.

    OpenAIRE

    Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...

  10. Landmarks in Insulin Research

    OpenAIRE

    Ward, Colin W.; Lawrence, Michael C.

    2011-01-01

    Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor.

  11. Human ultralente insulin.

    OpenAIRE

    Holman, R R; Steemson, J; Darling, P; Reeves, W G; Turner, R.C.

    1984-01-01

    The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). Ther...

  12. Cardiac remodelling and RAS inhibition.

    Science.gov (United States)

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  13. Binding of insulin to rat pancreatic islets: comparison between pancreatic human insulin and biosynthetic human insulin

    Energy Technology Data Exchange (ETDEWEB)

    Verspohl, E.J.; Ammon, H.P.

    Human pancreatic insulin, biosynthetic human insulin (BHI), and pork insulin were compared in terms of their binding characteristics to insulin receptors on rat pancreatic islets. There was no difference in binding or on biologic effect, i.e., ability to inhibit insulin secretion.

  14. Insulin action in human thighs after one-legged immobilization

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Mizuno, M.;

    1989-01-01

    Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH......-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine...... release of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I...

  15. Medanta insulin protocols in patients undergoing cardiac surgery

    Directory of Open Access Journals (Sweden)

    Beena Bansal

    2014-01-01

    Full Text Available Hyperglycemia is common in patients undergoing cardiac surgery and is associated with poor outcomes. This is a review of the perioperative insulin protocol being used at Medanta, the Medicity, which has a large volume cardiac surgery setup. Preoperatively, patients are usually continued on their preoperative outpatient medications. Intravenous insulin infusion is intiated postoperatively and titrated using a column method with a choice of 7 scales. Insulin dose is calculated as a factor of blood glucose and patient′s estimated insulin sensitivity. A comparison of this protocol is presented with other commonly used protocols. Since arterial blood gas analysis is done every 4 hours for first two days after cardiac surgery, automatic data collection from blood gas analyzer to a central database enables collection of glucose data and generating glucometrics. Data auditing has helped in improving performance through protocol modification.

  16. Rule-based model of vein graft remodeling.

    Directory of Open Access Journals (Sweden)

    Minki Hwang

    Full Text Available When vein segments are implanted into the arterial system for use in arterial bypass grafting, adaptation to the higher pressure and flow of the arterial system is accomplished thorough wall thickening and expansion. These early remodeling events have been found to be closely coupled to the local hemodynamic forces, such as shear stress and wall tension, and are believed to be the foundation for later vein graft failure. To further our mechanistic understanding of the cellular and extracellular interactions that lead to global changes in tissue architecture, a rule-based modeling method is developed through the application of basic rules of behaviors for these molecular and cellular activities. In the current method, smooth muscle cell (SMC, extracellular matrix (ECM, and monocytes are selected as the three components that occupy the elements of a grid system that comprise the developing vein graft intima. The probabilities of the cellular behaviors are developed based on data extracted from in vivo experiments. At each time step, the various probabilities are computed and applied to the SMC and ECM elements to determine their next physical state and behavior. One- and two-dimensional models are developed to test and validate the computational approach. The importance of monocyte infiltration, and the associated effect in augmenting extracellular matrix deposition, was evaluated and found to be an important component in model development. Final model validation is performed using an independent set of experiments, where model predictions of intimal growth are evaluated against experimental data obtained from the complex geometry and shear stress patterns offered by a mid-graft focal stenosis, where simulation results show good agreements with the experimental data.

  17. Diabetes Mellitus, Arterial Wall, and Cardiovascular Risk Assessment

    Science.gov (United States)

    Kozakova, Michaela; Palombo, Carlo

    2016-01-01

    Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structural background for cardiovascular events. The present paper provides a critical overview of the clinical evidence linking diabetes-related metabolic abnormalities to cardiovascular risk, debates the pathophysiologic mechanisms through which insulin resistance and hyperglycemia may affect the arterial wall, and discusses the associations between vascular biomarkers, metabolic abnormalities and cardiovascular events. PMID:26861377

  18. Characteristics of arterial hypertension in obesity

    Directory of Open Access Journals (Sweden)

    Ivković-Lazar Tatjana A.

    2004-01-01

    Full Text Available Introduction Arterial hypertension is the most frequent cardiovascular disease in obese persons, progressing with time to left ventricular hypertension, often associated with dilatation, diastolic disorders, hearth rhythm disturbance, and generalized atherosclerosis. Etiology The origin of this disease is related to hemodynamic disturbances (increased blood volume, minute volume, mainly due to increased stroke volume accompanied with changes of peripheral resistance, which increases in a later phase. However, metabolic factors are presently considered as primarily responsible for appearance of hypertension, which has rightly obtained the attribute of metabolic hypertension. A key role belongs to insulin, in fact, to insulin resistance and hyperinsulinism. Treatment Awareness of the metabolic basis of arterial hypertension in obesity has resulted in a specific approach to its treatment. The primary treatment includes reduction diet, with a drastic reduction of salt intake and with compulsory physical activity, while concerning medications one should consider converting enzyme inhibitors, alpha1 blockers and calcium channel antagonists. .

  19. Alternative Devices for Taking Insulin

    Science.gov (United States)

    ... KB). Alternate Language URL Alternative Devices for Taking Insulin Page Content On this page: What alternative devices ... the skin. [ Top ] What alternative devices for taking insulin are available? Insulin pens provide a convenient, easy- ...

  20. Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Sakao, Seiichiro; Voelkel, Norbert F; Tanabe, Nobuhiro; Tatsumi, Koichiro

    2015-01-01

    Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

  1. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Mai, Francesca; Martella, Letizia; De Feo, Martina; Soddu, Daniele; Fellini, Emanuela; Veneri, Mariangela; Stamerra, Cosimo A; Ferri, Claudio

    2015-11-18

    Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases.

  2. Anaphylaxis to protamine masquerading as an insulin allergy.

    Science.gov (United States)

    Kim, R

    1993-01-01

    This is the case of a 62-year-old man referred for the evaluation of insulin allergy. This patient had reacted to the subcutaneous injection of Novolin 70/30 (Squibb, Princeton, N.J.) and Humulin NPH (Eli Lilly, Indianapolis, Ind.). These reactions were characterized by the immediate onset of diffuse pruritic urticaria and angioedema with progression to hypotension as well as a local reaction. Past history also included anaphylactic shock after intravenous administration of protamine sulfate used for heparin reversal during arterial bypass surgery. Immediate hypersensitivty skin testing to protamine containing (NPH) insulin and protamine sulfate USP were strongly positive, while Lente insulin (Eli Lilly, Indianapolis, Ind.) and controls were negative. RAST tests revealed the titers > 24 ng/ml of protamine specific IgE with 98 percent inhibition and 1163 ng/ml of protamine specific IgG with 29 percent inhibition, while levels of insulin specific antibodies were negligible. Subsequently, the patient was treated with non-protamine containing insulin preparation, Lente insulin, without further incident. This study confirms the diagnosis of Type I hypersensitivity to protamine sulfate masquerading as insulin allergy. PMID:8454092

  3. Distinct right ventricle remodeling in response to pressure overload in the rat.

    Science.gov (United States)

    Mendes-Ferreira, P; Santos-Ribeiro, D; Adão, R; Maia-Rocha, C; Mendes-Ferreira, M; Sousa-Mendes, C; Leite-Moreira, A F; Brás-Silva, C

    2016-07-01

    Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. PMID:27199115

  4. A fly's view of neuronal remodeling.

    Science.gov (United States)

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  5. Multidetector computed tomography predictors of late ventricular remodeling and function after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Lessick, Jonathan, E-mail: j_lessick@rambam.health.gov.il [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Abadi, Sobhi [Medical Imaging Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Agmon, Yoram [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Keidar, Zohar [Nuclear Medicine Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Carasso, Shemi; Aronson, Doron [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Ghersin, Eduard [Department of Diagnostic Radiology, University of Miami, Miller School of Medicine, Miami, FL (United States); Rispler, Shmuel [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Sebbag, Anat [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Israel, Ora [Nuclear Medicine Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Hammerman, Haim; Roguin, Ariel [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel)

    2012-10-15

    Background: Despite advent of rapid arterial revascularization as 1st line treatment for acute myocardial infarction (AMI), incomplete restoral of flow at the microvascular level remains a problem and is associated with adverse prognosis, including pathological ventricular remodeling. We aimed to study the association between multidetector row computed tomography (MDCT) perfusion defects and ventricular remodeling post-AMI. Methods: In a prospective study, 20 patients with ST-elevation AMI, treated by primary angioplasty, underwent arterial and late phase MDCT as well as radionuclide scans to study presence, size and severity of myocardial perfusion defects. Contrast echocardiography was performed at baseline and at 4 months follow-up to evaluate changes in myocardial function and remodeling. Results: Early defects (ED), late defects (LD) and late enhancement (LE) were detected in 15, 7 and 16 patients, respectively and radionuclide defects in 15 patients. The ED area (r = 0.74), and LD area (r = 0.72), and to a lesser extent LE area (r = 0.62) correlated moderately well with SPECT summed rest score. By univariate analysis, follow-up end-systolic volume index and ejection fraction were both significantly related to ED and LD size and severity, but not to LE size or severity. By multivariate analysis, end-systolic volume index was best predicted by LD area (p < 0.05) and ejection fraction by LD enhancement ratio. Conclusions: LD size and severity on MDCT are most closely associated with pathological ventricular remodeling after AMI and may thus play a role in early identification and treatment of this condition.

  6. Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2+/− Mice with Schistosomiasis

    Science.gov (United States)

    Soon, Elaine; Jones, Frances M.; Southwood, Mark R.; Haghighat, Leila; Toshner, Mark R.; Raine, Tim; Horan, Ian; Yang, Peiran; Moore, Stephen; Ferrer, Elisabet; Wright, Penny; Ormiston, Mark L.; White, R. James; Haight, Deborah A.; Dunne, David W.

    2015-01-01

    Rationale: Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are the commonest genetic cause of PAH. Objectives: To determine whether Bmpr2+/− mice are more susceptible to schistosomiasis-induced pulmonary vascular remodeling. Methods: Wild-type (WT) and Bmpr2+/− mice were infected percutaneously with Schistosoma mansoni. At 17 weeks postinfection, right ventricular systolic pressure and liver and lung egg counts were measured. Serum, lung and liver cytokine, pulmonary vascular remodeling, and liver histology were assessed. Measurements and Main Results: By 17 weeks postinfection, there was a significant increase in pulmonary vascular remodeling in infected mice. This was greater in Bmpr2+/− mice and was associated with an increase in egg deposition and cytokine expression, which induced pulmonary arterial smooth muscle cell proliferation, in the lungs of these mice. Interestingly, Bmpr2+/− mice demonstrated dilatation of the hepatic central vein at baseline and postinfection, compared with WT. Bmpr2+/− mice also showed significant dilatation of the liver sinusoids and an increase in inflammatory cells surrounding the central hepatic vein, compared with WT. This is consistent with an increase in the transhepatic passage of eggs. Conclusions: This study has shown that levels of BMPR-II expression modify the pulmonary vascular response to chronic schistosomiasis. The likely mechanism involves the increased passage of eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids in Bmpr2+/− mice. Genetically determined differences in the remodeling of hepatic vessels may represent a new risk factor for PAH associated with schistosomiasis. PMID:26308618

  7. Multidetector computed tomography predictors of late ventricular remodeling and function after acute myocardial infarction

    International Nuclear Information System (INIS)

    Background: Despite advent of rapid arterial revascularization as 1st line treatment for acute myocardial infarction (AMI), incomplete restoral of flow at the microvascular level remains a problem and is associated with adverse prognosis, including pathological ventricular remodeling. We aimed to study the association between multidetector row computed tomography (MDCT) perfusion defects and ventricular remodeling post-AMI. Methods: In a prospective study, 20 patients with ST-elevation AMI, treated by primary angioplasty, underwent arterial and late phase MDCT as well as radionuclide scans to study presence, size and severity of myocardial perfusion defects. Contrast echocardiography was performed at baseline and at 4 months follow-up to evaluate changes in myocardial function and remodeling. Results: Early defects (ED), late defects (LD) and late enhancement (LE) were detected in 15, 7 and 16 patients, respectively and radionuclide defects in 15 patients. The ED area (r = 0.74), and LD area (r = 0.72), and to a lesser extent LE area (r = 0.62) correlated moderately well with SPECT summed rest score. By univariate analysis, follow-up end-systolic volume index and ejection fraction were both significantly related to ED and LD size and severity, but not to LE size or severity. By multivariate analysis, end-systolic volume index was best predicted by LD area (p < 0.05) and ejection fraction by LD enhancement ratio. Conclusions: LD size and severity on MDCT are most closely associated with pathological ventricular remodeling after AMI and may thus play a role in early identification and treatment of this condition

  8. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    OpenAIRE

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  9. Vascular remodeling in the growth hormone transgenic mouse.

    Science.gov (United States)

    Dilley, R J; Schwartz, S M

    1989-11-01

    Using mice transgenic for the growth hormone gene (TGHM), we have studied the effects of a systemic elevation of growth hormone on vascular growth with the aim of investigating the role of vascular mass changes in producing hypertension. In contrast to human acromegaly or gigantism, there was no elevation of blood pressure in TGHM, but there were significant increases in vascular wall mass. In accordance with a presumably increased perfusion of larger organs, the medial cross-sectional areas of thoracic aorta and mesenteric resistance vessels were greater in the TGHM. These differences could be normalized in the aorta by body weight and in the mesenteric vessel by small intestine weight. Furthermore, the brain was not significantly heavier in the TGHM, and their carotid and cerebral vessels also were not larger. Wall-to-lumen ratios were similar in the aorta, carotid, and middle cerebral arteries suggesting that wall stress was the controlling factor in wall thickness. Surprisingly, the mesenteric vessels had increased wall-to-lumen ratio, which was similar to that seen in hypertensive vascular remodeling but in a normotensive animal. In an attempt to explain this finding it was noted that the pattern of mesenteric vascular networks and even organized structure within the vessel wall itself appeared to be fixed, perhaps by genetic mechanisms. Thus, vascular network structure may be a potentially limiting factor in the ability of the vessel wall to remodel and may have been responsible for the greater wall-to-lumen ratio in TGHM mesenteric vessels. A similar situation in human acromegaly or gigantism could result in a circulation marginally able to correct for other demands on blood flow resulting in about one third of cases being hypertensive. PMID:2805241

  10. VASCULAR REMODELING AND HEART RATE VARIABILITY IN DIFFERENT ANTIHYPERTENSIVE THERAPIES

    Directory of Open Access Journals (Sweden)

    E. D. Golovanova

    2008-01-01

    Full Text Available Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d, metoprolol tartrate (Egilok Retard, 50 mg/d and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg on pulse wave velocity (PWV, cardio-ankle vascular index (CAVI and the sympathetic system activity.Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades were examined. Biological age (BA was determined by the linear regression and the vascular wall age (VWA was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan. 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV were determined before and at the end of the therapies.Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

  11. Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

    DEFF Research Database (Denmark)

    Barascuk, N; Vassiliadis, E; Zheng, Qiuju;

    2011-01-01

    Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA)......) developed to measure a specific MMP12-derived fragment of mimecan, MMCN-151, in apolipoprotein-E knockout (ApoE-KO) mice....

  12. Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice

    Institute of Scientific and Technical Information of China (English)

    张健

    2014-01-01

    Objective To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice.Methods Myocardial infarction(MI)was induced in mice by left coronary artery ligation.Mice were randomly assigned to sham operation group(n=6),PDE5shRNA group(n=12),common adenovirus group(n=15)and DMEM group(n=8).Four weeks post-MI,the survival rate was evaluated.

  13. HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction

    OpenAIRE

    Labrousse-Arias, David; Castillo-González, Raquel; Rogers, Natasha M.; Torres-Capelli, Mar; Barreira, Bianca; Aragonés, Julián; Cogolludo, Ángel; Isenberg, Jeffrey S.; Calzada, María J.

    2015-01-01

    Aims Hypoxic conditions stimulate pulmonary vasoconstriction and vascular remodelling, both pathognomonic changes in pulmonary arterial hypertension (PAH). The secreted protein thrombospondin-1 (TSP1) is involved in the maintenance of lung homeostasis. New work identified a role for TSP1 in promoting PAH. Nonetheless, it is largely unknown how hypoxia regulates TSP1 in the lung and whether this contributes to pathological events during PAH. Methods and results In cell and animal experiments, ...

  14. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

    Directory of Open Access Journals (Sweden)

    Hassan Mziaut

    2016-08-01

    Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion.

  15. Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKα2

    DEFF Research Database (Denmark)

    de Boer, Michiel P; Meijer, Rick I; Richter, Erik;

    2016-01-01

    Decreased tissue perfusion increases the risk of developing insulin resistance and cardiovascular disease in obesity, and decreased levels of globular adiponectin (gAdn) have been proposed to contribute to this risk. We hypothesized that gAdn controls insulin's vasoactive effects through AMP......-activated protein kinase (AMPK), specifically its α2 subunit, and studied the mechanisms involved. In healthy volunteers, we found that decreased plasma gAdn levels in obese subjects associate with insulin resistance and reduced capillary perfusion during hyperinsulinemia. In cultured human microvascular...... endothelial cells (HMEC), gAdn increased AMPK activity. In isolated muscle resistance arteries gAdn uncovered insulin-induced vasodilation by selectively inhibiting insulin-induced activation of ERK1/2, and the AMPK inhibitor compound C as well as genetic deletion of AMPKα2 blunted insulin...

  16. KLF5 mediates vascular remodeling via HIF-1α in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Li, Xiaochen; He, Yuanzhou; Xu, Yongjian; Huang, Xiaomin; Liu, Jin; Xie, Min; Liu, Xiansheng

    2016-02-15

    Hypoxic pulmonary hypertension (HPH) is characterized by active vasoconstriction and profound vascular remodeling. KLF5, a zinc-finger transcription factor, is involved in the excessive proliferation and apoptotic resistance phenotype associated with monocrotaline-induced pulmonary hypertension. However, the molecular mechanisms of KLF5-mediated pathogenesis of HPH are largely undefined. Adult male Sprague-Dawley rats were exposed to normoxia or hypoxia (10% O2) for 4 wk. Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased right ventricular systolic pressure. The levels of KLF5 and hypoxia-inducible factor-1α (HIF-1α) were upregulated in distal pulmonary arterial smooth muscle from hypoxic rats. The knockdown of KLF5 via short-hairpin RNA attenuated chronic hypoxia-induced hemodynamic and histological changes in rats. The silencing of either KLF5 or HIF-1α prevented hypoxia-induced (5%) proliferation and migration and promoted apoptosis in human pulmonary artery smooth muscle cells. KLF5 was immunoprecipitated with HIF-1α under hypoxia and acted as an upstream regulator of HIF-1α. The cell cycle regulators cyclin B1 and cyclin D1 and apoptosis-related proteins including bax, bcl-2, survivin, caspase-3, and caspase-9, were involved in the regulation of KLF5/HIF-1α-mediated cell survival. This study demonstrated that KLF5 plays a crucial role in hypoxia-induced vascular remodeling in an HIF-1α-dependent manner and provided a better understanding of the pathogenesis of HPH. PMID:26702149

  17. Angioplasty and stent placement -- peripheral arteries

    Science.gov (United States)

    Percutaneous transluminal angioplasty - peripheral artery; PTA - peripheral artery; Angioplasty - peripheral arteries; Iliac artery -angioplasty; Femoral artery - angioplasty; Popliteal artery - angioplasty; Tibial ...

  18. Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.

    Science.gov (United States)

    Wascher, T C; Wölkart, G; Russell, J C; Brunner, F

    2000-05-01

    Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat, which exhibits the metabolic syndrome of obesity, insulin resistance, hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these alterations served as controls. Animals of both groups were normotensive (mean arterial pressure 136+/-2 mmHg). Hearts from obese and lean rats aged 7 (n = 6) or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51 min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a validated method, and interstitial insulin was determined with a radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both experimental groups (half-times of transfer: 11+/-0.2 min in obese and 18+/-4 min in lean rats; NS), but at 0.5 U/l, the respective half-times were 7+/-1 min in lean and 13+/-2 min in obese rats (P < 0.05). The steady-state level of insulin in the interstitium was 34+/-1% of the vascular level at 0.1 U/l and reached the vascular level (102+/-2%) at 0.5 U/l in both lean and obese rats. In rats aged 18 weeks, the half-times of insulin transfer were 31+/-2 and 14+/-l min in obese rats and 10+/-0.3 and 7+/-0.3 min in lean rats (P < 0.05). Again, interstitial steady-state levels were similar in both groups. Finally, postprandial insulin dynamics were simulated over a period of 120 min with a peak concentration of 0.8 U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38+/-0.02 U/l in lean rats and 0.24+/-0.02 U/l in obese rats (P < 0.05), and a similar difference was noted throughout insulin infusion (areas under the transudate concentration-time curves: 17 and 11 U

  19. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  20. The skeleton in the closet: actin cytoskeletal remodeling in β-cell function.

    Science.gov (United States)

    Arous, Caroline; Halban, Philippe A

    2015-10-01

    Over the last few decades, biomedical research has considered not only the function of single cells but also the importance of the physical environment within a whole tissue, including cell-cell and cell-extracellular matrix interactions. Cytoskeleton organization and focal adhesions are crucial sensors for cells that enable them to rapidly communicate with the physical extracellular environment in response to extracellular stimuli, ensuring proper function and adaptation. The involvement of the microtubular-microfilamentous cytoskeleton in secretion mechanisms was proposed almost 50 years ago, since when the evolution of ever more sensitive and sophisticated methods in microscopy and in cell and molecular biology have led us to become aware of the importance of cytoskeleton remodeling for cell shape regulation and its crucial link with signaling pathways leading to β-cell function. Emerging evidence suggests that dysfunction of cytoskeletal components or extracellular matrix modification influences a number of disorders through potential actin cytoskeleton disruption that could be involved in the initiation of multiple cellular functions. Perturbation of β-cell actin cytoskeleton remodeling could arise secondarily to islet inflammation and fibrosis, possibly accounting in part for impaired β-cell function in type 2 diabetes. This review focuses on the role of actin remodeling in insulin secretion mechanisms and its close relationship with focal adhesions and myosin II.

  1. A superactive insulin: [B10-aspartic acid]insulin(human).

    OpenAIRE

    Schwartz, G P; Burke, G. T.; Katsoyannis, P G

    1987-01-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. We have synthesized a human insulin analogue, [AspB10]insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [AspB10]Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +/- 14...

  2. Carotid Artery Disease

    Science.gov (United States)

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  3. Peripheral arterial line (image)

    Science.gov (United States)

    A peripheral arterial line is a small, short plastic catheter placed through the skin into an artery of the arm or leg. The purpose of a peripheral arterial line is to allow continuous monitoring of ...

  4. Why do anti-inflammatory therapies fail to improve insulin sensitivity?

    Institute of Scientific and Technical Information of China (English)

    Zhan-guo GAO; Jian-ping YE

    2012-01-01

    Chronic inflammation occurs in obese conditions in both humans and animals.It also contributes to the pathogenesis of type 2 diabetes (T2D) through insulin resistance,a status in which the body loses its ability to respond to insulin.Inflammation impairs insulin signaling through the functional inhibition of IRS-1 and PPARy.Insulin sensitizers (such as rosiglitazone and pioglitazone) inhibit inflammation while improving insulin sensitivity.Therefore,anti-inflammatory agents have been suggested as a treatment strategy for insulin resistance.This strategy has been tested in laboratory studies and clinical trials for more than 10 years; however,no significant progress has been made in any of the model systems.This status has led us to re-evaluate the biological significance of chronic inflammation in obesity.Recent studies have consistently asserted that obesity-associated inflammation helps to maintain insulin sensitivity.Inflammation stimulates local adipose tissue remodeling and promotes systemic energy expenditure.We propose that these beneficial activities of inflammation provide an underlying mechanism for the failure of anti-infiammatory therapy in the treatment of insulin resistance.Current literature will be reviewed in this article to present evidence that supports this viewpoint.

  5. Insulin glulisine: insulin receptor signaling characteristics in vivo.

    Science.gov (United States)

    Hennige, Anita M; Lehmann, Rainer; Weigert, Cora; Moeschel, Klaus; Schäuble, Myriam; Metzinger, Elisabeth; Lammers, Reiner; Häring, Hans-Ulrich

    2005-02-01

    In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular insulin in mealtime supplementation. However, safety issues have been raised with these alternatives, as the alteration of the three-dimensional structure may alter the interaction with the insulin and/or IGF-I receptors and therefore lead to the activation of alternate metabolic as well as mitogenic signaling pathways. It is therefore essential to carefully study acute and long-term effects in a preclinical state, as insulin therapy is meant to be a lifelong treatment. In this study, we determined in vivo the insulin receptor signaling characteristics activated by insulin glulisine (Lys(B3), Glu(B29)) at the level of insulin receptor phosphorylation, insulin receptor substrate phosphorylation, and downstream signaling elements such as phosphatidylinositol (PI) 3-kinase, AKT, and mitogen-activated protein kinase. C57BL/6 mice were injected with insulin glulisine or regular insulin and Western blot analysis was performed for liver and muscle tissue. The extent and time course of insulin receptor phosphorylation and activation of downstream signaling elements after insulin glulisine treatment was similar to that of human regular insulin in vivo. Moreover, insulin signaling in hypothalamic tissue determined by PI 3-kinase activity was comparable. Therefore, insulin glulisine may be a useful tool for diabetes treatment. PMID:15677493

  6. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  7. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  8. Inflammation in pulmonary arterial hypertension.

    Science.gov (United States)

    Price, Laura C; Wort, S John; Perros, Frédéric; Dorfmüller, Peter; Huertas, Alice; Montani, David; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2012-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study. PMID:22215829

  9. Brachytherapy in coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medicine School, Gwangju (Korea, Republic of)

    2006-04-15

    Coronary artery disease is a leading cause of morbidity and mortality across the world. Percutaneous coronary intervention has become the major technique of revascularization. However, restenosis remains a major limitation of this procedure. Recently the need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction to two major advances, intracoronary brachytherapy and the drug-eluting stents, intracoronary brachytherapy has been employed in recent years to prevent restenosis lesions with effective results, principally in in-stent restenosis. Restenosis is generally considered as an excessive form of normal wound healing divided up in processes: elastic recoil, neointimal hyperplasia, and negative vascular remodeling. Restenosis has previously been regarded as a proliferative process in which neointimal thickening, mediated by a cascade of inflammatory mediators and other factors, is the key factor. Ionizing radiation has been shown to decrease the proliferative response to injury in animal models of restenosis. Subsequently, several randomized, double-blind trials have demonstrated that intracoronary brachytherapy can reduce the rates to both angiographic restenosis and clinical event rates in patients undergoing percutaneous coronary intervention for in-stent restenosis. Some problems, such as late thrombosis and edge restenosis, have been identified as limiting factors of this technique. Brachytherapy is a promising method of preventing and treating coronary artery restenosis.

  10. Connexin Remodeling Contributes to Atrial Fibrillation

    OpenAIRE

    Michelle M Jennings; J Kevin Donahue

    2013-01-01

    Atrial fibrillation significantly contributes to mortality and morbidity through increased risk of stroke, heart failure and myocardial infarcts. Investigations of mechanisms responsible for the development and maintenance of atrial fibrillation have highlighted the importance of gap junctional remodeling. Connexins 40 and 43, the major atrial gap junctional proteins, undergo considerable alterations in expression and localization in atrial fibrillation, creating an environment conducive to s...

  11. Revealing remodeler function: Varied and unique

    Science.gov (United States)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  12. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  13. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  14. Re-Modelling as De-Professionalisation

    Science.gov (United States)

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  15. Management of pulmonary arterial hypertension.

    Science.gov (United States)

    McLaughlin, Vallerie V; Shah, Sanjiv J; Souza, Rogerio; Humbert, Marc

    2015-05-12

    Pulmonary hypertension (PH) is common and may result from a number of disorders, including left heart disease, lung disease, and chronic thromboembolic disease. Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure. Over the past decades, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options has exploded. A thorough evaluation of a patient is critical to correctly characterize the PH. Cardiac studies, including echocardiography and right heart catheterization, are key elements in the assessment. Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management. This review also underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach.

  16. Potassium channels in pulmonary arterial hypertension.

    Science.gov (United States)

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien

    2015-10-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH. PMID:26341985

  17. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand;

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  18. Advances in nanotechnology for the management of coronary artery disease.

    Science.gov (United States)

    Rhee, June-Wha; Wu, Joseph C

    2013-02-01

    Nanotechnology holds tremendous potential to advance the current treatment of coronary artery disease. Nanotechnology may assist medical therapies by providing a safe and efficacious delivery platform for a variety of drugs aimed at modulating lipid disorders, decreasing inflammation and angiogenesis within atherosclerotic plaques, and preventing plaque thrombosis. Nanotechnology may improve coronary stent applications by promoting endothelial recovery on a stent surface utilizing bio-mimetic nanofibrous scaffolds, and also by preventing in-stent restenosis using nanoparticle-based delivery of drugs that are decoupled from stents. Additionally, nanotechnology may enhance tissue-engineered graft materials for application in coronary artery bypass grafting by facilitating cellular infiltration and remodeling of a graft matrix.

  19. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ...

  20. Insulin Human Inhalation

    Science.gov (United States)

    ... control pills); oral medications for diabetes such as pioglitazone (Actos, in Actoplus Met, in Duetact, in Oseni) or ... or lower legs sudden weight gain extreme drowsiness confusion dizziness Insulin inhalation may increase the risk that ...

  1. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ... also helps a person lose weight control blood glucose levels control blood pressure control cholesterol levels People in the ...

  2. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob;

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis...

  3. Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension

    OpenAIRE

    Farha Samar; Laskowski Daniel; George Deepa; Park Margaret M; Tang WH Wilson; Dweik Raed A; Erzurum Serpil C

    2013-01-01

    Abstract Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in c...

  4. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

    OpenAIRE

    Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kulkarni, Rohit Narayan; Goldfine, Allison Braunwald

    2012-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, a...

  5. Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

    Energy Technology Data Exchange (ETDEWEB)

    Fernqvist-Forbes, E.; Linde, B.; Gunnarsson, R.

    1988-09-01

    We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U /sup 125/I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of /sup 125/I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir (mean, 2.0 +/- 0.1 (+/- SE) mmol/L) occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the (/sup 125/I)insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.

  6. Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

    International Nuclear Information System (INIS)

    We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U 125I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of 125I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir [mean, 2.0 +/- 0.1 (+/- SE) mmol/L] occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the [125I]insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF

  7. Myocardial autophagy activation and suppressed survival signaling is associated with insulin resistance in fructose-fed mice.

    Science.gov (United States)

    Mellor, Kimberley M; Bell, James R; Young, Morag J; Ritchie, Rebecca H; Delbridge, Lea M D

    2011-06-01

    Fructose intake is linked with the increasing prevalence of insulin resistance and there is now evidence for a specific insulin-resistant cardiomyopathy. The aim of this study was to determine the cardiac-specific myocardial remodeling effects of high fructose dietary intake. Given the links between insulin signaling, reactive oxygen species generation and autophagy induction, we hypothesized that autophagy contributes to pathologic remodeling in the insulin-resistant heart, and in particular may be a feature of high fructose diet-induced cardiac phenotype. Male C57Bl/6 mice were fed a high fructose (60%) diet or nutrient-matched control diet for 12 weeks. Systemic and myocardial insulin-resistant status was characterized. Superoxide production (lucigenin) and cellular growth and death signaling pathways were examined in myocardial tissue. Myocardial structural remodeling was evaluated by measurement of heart weight indices and histological analysis of collagen deposition (picrosirius red). Fructose-fed mice exhibited hyperglycemia and glucose intolerance, but plasma insulin and blood pressure were unchanged. High fructose intake suppressed the myocardial Akt cell survival signaling coincident with increased cardiac superoxide generation (21% increase, pFructose feeding induced elevated autophagy (LC3B-II: LC3B-I ratio: 46% increase, pfructose-fed mice. We provide the first evidence that myocardial autophagy activation is associated with systemic insulin resistance, and that high level fructose intake inflicts direct cardiac damage. Upregulated autophagy is associated with elevated cardiac superoxide production, suppressed cell survival signaling and fibrotic infiltration in fructose-fed mice. The novel finding that autophagy contributes to cardiac pathology in insulin resistance identifies a new therapeutic target for diabetic cardiomyopathy.

  8. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2010-01-01

    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  9. Insulin allergy treated with human insulin (recombinant DNA).

    Science.gov (United States)

    De Leeuw, I; Delvigne, C; Bekaert, J

    1982-01-01

    Two insulin-dependent diabetic subjects treated with pork and beef insulin during a period of 6 mo developed severe local reactions. Both patients had an important allergic history (asthma, urticaria, drug reactions, rhinitis). Skin-testing revealed type I allergy to beef and pork insulin. Specific IgE-insulin binding was demonstrated with both insulins. After negative skin testing with NPH Lilly human insulin (recombinant DNA), treatment was started with this compound and remained successful during a period of 6-9 mo. In one patient a local reaction occurred when regular human insulin (recombinant DNA) was added to NPH in order to obtain better control. Skin testing with regular human insulin was positive, but not with NPH human insulin alone. The mechanism of this phenomenon remains unsolved. PMID:6765530

  10. Etiopathogenesis of Insulin Autoimmunity

    Directory of Open Access Journals (Sweden)

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  11. Conformational Dynamics of Insulin

    Directory of Open Access Journals (Sweden)

    Qing-xin eHua

    2011-10-01

    Full Text Available We have exploited a prandial insulin analogue (insulin lispro, the active component of Humalog®; Eli Lilly and Co. to elucidate the underlying structure and dynamics of insulin as a monomer in solution. Whereas NMR-based modeling recapitulates structural relationships of insulin crystals (T-state protomers, dynamic anomalies are revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics exist only at a subset of four -helical sites (two per chain flanking an internal disulfide bridge (cystine A20-B19; these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that dynamic re-engineering of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world.

  12. Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

    OpenAIRE

    Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

    2015-01-01

    Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, i...

  13. Differential Effects of Diet-Induced Dyslipidemia and Hyperglycemia on Mesenteric Resistance Artery Structure and Function in Type 2 Diabetes

    OpenAIRE

    Sachidanandam, Kamakshi; Hutchinson, Jim R.; Elgebaly, Mostafa M.; Mezzetti, Erin M; Wang, Mong-Heng; Ergul, Adviye

    2008-01-01

    Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and ma...

  14. Association of adiponectin gene polymorphism with adiponectin levels and risk for insulin resistance syndrome

    OpenAIRE

    Jai Prakash; Balraj Mittal; Shally Awasthi; Neena Srivastava

    2015-01-01

    Background: Adiponectin is an abundant adipose tissue-derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR). Methods: Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standar...

  15. Immunity in arterial hypertension: associations or causalities?

    Science.gov (United States)

    Anders, Hans-Joachim; Baumann, Marcus; Tripepi, Giovanni; Mallamaci, Francesca

    2015-12-01

    Numerous studies describe associations between markers of inflammation and arterial hypertension (aHT), but does that imply causality? Interventional studies that reduce blood pressure reduced also markers of inflammation, but does immunosuppression improve hypertension? Here, we review the available mechanistic data. Aberrant immunity can trigger endothelial dysfunction but is hardly ever the primary cause of aHT. Innate and adaptive immunity get involved once hypertension has caused vascular wall injury as immunity is a modifier of endothelial dysfunction and vascular wall remodelling. As vascular remodelling progresses, immunity-related mechanisms can become significant cofactors for cardiovascular (CV) disease progression; vice versa, suppressing immunity can improve hypertension and CV outcomes. Innate and adaptive immunity both contribute to vascular wall remodelling. Innate immunity is driven by danger signals that activate Toll-like receptors and other pattern-recognition receptors. Adaptive immunity is based on loss of tolerance against vascular autoantigens and includes autoreactive T-cell immunity as well as non-HLA angiotensin II type 1 receptor-activating autoantibodies. Such processes involve numerous other modulators such as regulatory T cells. Together, immunity is not causal for hypertension but rather an important secondary pathomechanism and a potential therapeutic target in hypertension.

  16. The RSC chromatin remodeling complex has a crucial role in the complete remodeler set for yeast PHO5 promoter opening.

    Science.gov (United States)

    Musladin, Sanja; Krietenstein, Nils; Korber, Philipp; Barbaric, Slobodan

    2014-04-01

    Although yeast PHO5 promoter chromatin opening is a founding model for chromatin remodeling, the complete set of involved remodelers remained unknown for a long time. The SWI/SNF and INO80 remodelers cooperate here, but nonessentially, and none of the many tested single or combined remodeler gene mutations could prevent PHO5 promoter opening. RSC, the most abundant and only remodeler essential for viability, was a controversial candidate for the unrecognized remodeling activity but unassessed in vivo. Now we show that remodels the structure of chromatin (RSC) is crucially involved in PHO5 promoter opening. Further, the isw1 chd1 double deletion also delayed chromatin remodeling. Strikingly, combined absence of RSC and Isw1/Chd1 or Snf2 abolished for the first time promoter opening on otherwise sufficient induction in vivo. Together with previous findings, we recognize now a surprisingly complex network of five remodelers (RSC, SWI/SNF, INO80, Isw1 and Chd1) from four subfamilies (SWI/SNF, INO80, ISWI and CHD) as involved in PHO5 promoter chromatin remodeling. This is likely the first described complete remodeler set for a physiological chromatin transition. RSC was hardly involved at the coregulated PHO8 or PHO84 promoters despite cofactor recruitment by the same transactivator and RSC's presence at all three promoters. Therefore, promoter-specific chromatin rather than transactivators determine remodeler requirements.

  17. Atrial Electrical Remodeling and Sleep Disordered Breathing

    Directory of Open Access Journals (Sweden)

    Adrian Baranchuk; Diego Conde

    2013-08-01

    Full Text Available To the Editor: We read with interest the article from Bitter et al. (1 published in the last volume of JAFIB. This non-systematic review covers some of the most important physiopathological aspects of the link between sleep disordered breathing (SDB and atrial fibrillation (AFib. We do agree with the authors on the role of hypertension, endothelial dysfunction and inflammation. These topics were, to our understanding and perspective, very well covered by the authors on this review. However, despite that the authors mentioned atrial remodeling a couple of times during their review, we are not sure that this topic and specifically atrial electrical remodeling, was properly discussed and referenced. The pathophysiology linking SDB to AF is multifactorial and may involve repetitive hypoxemia, increased sympathetic drive, fluctuations in intrathoracic pressure and systemic inflammation (2. These physiologic changes may induce structural and electrical remodeling serving as a substrate to the development of AFib. An indirect marker for such electrical remodeling is the prolongation of atrial conduction time, represented by increased maximum P-wave duration in the surface ECG. In a prior study, we showed that an increased P-wave duration has been associated with SDB (3. Interatrial block (IAB, defined as a surface P-wave duration > 120 ms, was more prevalent in patients with moderate-severe SDB (34.7% SDB vs. 0% controls, p 25 were independent predictors of maximum P-wave duration (p=0.001 and p<0.001 respectively (3. Another non-invasive method to determine atrial electrical remodeling is the Signal-averaged P-wave (SAPW duration. The SAPW duration represents the average of all P-wave durations in a given number of consecutive heartbeats. We recently postulated that SAPW would be useful to identify atrial electrical remodeling in patients with severe SDB and that treatment with C-PAP for 4-6 weeks may induce reverse atrial electrical remodeling (4

  18. Increased transvascular low density lipoprotein transport in insulin dependent diabetes

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo;

    2003-01-01

    accumulation and thus atherosclerosis. METHODS: We used an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 24 patients with insulin dependent diabetes mellitus (type 1) and in 30 healthy controls. LDL was individually sampled and autologous 131...... be increased in patients with type 1 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with type 1 diabetes, possibly explaining accelerated development of atherosclerosis....

  19. Influence of circulating epinephrine on absorption of subcutaneously injected insulin

    International Nuclear Information System (INIS)

    Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin

  20. Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension

    Science.gov (United States)

    Liu, Fei; Haeger, Christina Mallarino; Dieffenbach, Paul B.; Sicard, Delphine; Chrobak, Izabela; Coronata, Anna Maria F.; Suárez Velandia, Margarita M.; Vitali, Sally; Colas, Romain A.; Norris, Paul C.; Marinković, Aleksandar; Liu, Xiaoli; Ma, Jun; Rose, Chase D.; Lee, Seon-Jin; Comhair, Suzy A.A.; Erzurum, Serpil C.; McDonald, Jacob D.; Serhan, Charles N.; Walsh, Stephen R.; Tschumperlin, Daniel J.; Fredenburgh, Laura E.

    2016-01-01

    Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation. Atomic force microscopy microindentation demonstrated early PA stiffening in experimental PH and human lung tissue. Pulmonary artery smooth muscle cells (PASMC) grown on substrates with the stiffness of remodeled PAs showed increased proliferation, decreased apoptosis, exaggerated contraction, enhanced matrix deposition, and reduced COX-2–derived prostanoid production compared with cells grown on substrates approximating normal PA stiffness. Treatment with a prostaglandin I2 analog abrogated monocrotaline-induced PA stiffening and attenuated stiffness-dependent increases in proliferation, matrix deposition, and contraction in PASMC. Our results suggest a pivotal role for early PA stiffening in PH and demonstrate the therapeutic potential of interrupting mechanobiological feedback amplification of vascular remodeling in experimental PH. PMID:27347562

  1. [Risk factors for arterial disease].

    Science.gov (United States)

    Madoery, Roberto; Rubin, Graciela; Luquez, Hugo; Luquez, Cecilia; Cravero, Cecilia

    2004-01-01

    The risk factors of arterial disease (FREA) predict a future damage over the vascular system of the human body. Its detection are considered a key for the diagnostic as well as for the preventive and even curative strategies. For a long time, scientist considered those factors originated as a consecuence of large studies during the middle of the last century, with current validity up to our days. A simple classification spoke of them as traditionals. Further investigations described the so called new or emergents.factors that where joint together accordingly to their actions: coagulation factors, psicosocial, inflamatories and infectious. A recent classification, taking into account the type of impact, divided them into; causatives, predisposals and conditionals. Also, it was described a mechanism, the oxidative power, with consecuences over the endothelium, in the last part of the process. Before, another mechanism was described: the insulin resistance and the hiperinsulinism, bases for the Metabolic Syndrome, that includes a number of traditional risk factors.

  2. Elastin organization in pig and cardiovascular disease patients' pericardial resistance arteries

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas; Nissen, Inger;

    2015-01-01

    Peripheral vascular resistance is increased in essential hypertension. This involves structural changes of resistance arteries and stiffening of the arterial wall, including remodeling of the extracellular matrix. We hypothesized that biopsies of the human parietal pericardium, obtained during...... coronary artery bypass grafting or cardiac valve replacement surgeries, can serve as a source of resistance arteries for structural research in cardiovascular disease patients. We applied two-photon excitation fluorescence microscopy to study the parietal pericardium and isolated pericardial resistance...... of 100 mm Hg) is fiber like, and no prominent external elastic lamina could be observed. This microarchitecture is very different from that in rat mesenteric arteries frequently used for resistance artery research. In conclusion, we add three-dimensional information on the structure of the extracellular...

  3. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  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. Myocardial connective tissue growth factor (CCN2/CTGF attenuates left ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Jørgen Gravning

    Full Text Available AIMS: Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV remodeling after myocardial infarction (MI remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI. METHODS AND RESULTS: Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF and non-transgenic littermate controls (NLC were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42 admitted to hospital for percutaneous coronary intervention (PCI serum-CTGF levels (s-CTGF were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15. CONCLUSION: Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.

  6. Chemical and thermal stability of insulin

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B;

    2006-01-01

    To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands.......To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands....

  7. Cell wall remodeling under abiotic stress

    OpenAIRE

    Tenhaken, Raimund

    2015-01-01

    Plants exposed to abiotic stress respond to unfavorable conditions on multiple levels. One challenge under drought stress is to reduce shoot growth while maintaining root growth, a process requiring differential cell wall synthesis and remodeling. Key players in this process are the formation of reactive oxygen species (ROS) and peroxidases, which initially cross-link phenolic compounds and glycoproteins of the cell walls causing stiffening. The function of ROS shifts after having converted a...

  8. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J. Fred; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  9. Acute Aerobic Exercise and Plasma Levels of Orexin A, Insulin, Glucose, and Insulin Resistance in Males With Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alizadeh

    2016-01-01

    Full Text Available Background The endocrine system disruptions are the main factors in metabolic disorders which are due to lifestyle changes, obesity, and aging. Insulin resistance is impaired glucose homeostasis in the presence of insulin and is related to many diseases such as hypertension, coronary artery disease, and type 2 diabetes Objectives This study aimed to investigate the effect of acute aerobic exercise on plasma levels of orexin A, insulin, glucose, and insulin resistance in males with type 2 diabetes. Patients and Methods Twenty subjects (mean age = 45.40 ± 5.42 years, mean weight = 80.91 ± 6.35 kg, body mass index = 25.41 ± 2.76 kg/m2 were randomly assigned into control and experimental groups, involving 10 people in each group. The exercise protocol consisted of one session of acute aerobic exercise on a treadmill at 60% maximal oxygen uptake and the same energy expenditure (300 kcal, which were determined by gas analyzers. Subjects were subjected to samplings before, immediately after, and 24 hours after the acute aerobic exercise. Results The analysis of findings in P ≤ 0.05 indicated that acute aerobic exercise caused a significant increase in plasma levels of orexin A and a significant decrease in plasma levels of glucose immediately after the aerobic activity, but insignificantly affected the plasma levels of insulin and insulin resistance. Conclusions It seems that in people with type 2 diabetes, acute aerobic exercise can decrease the plasma levels of glucose, possibly through increasing orexin A. In addition, negative energy balance is necessary to decrease the levels of insulin and insulin resistance during acute aerobic exercise.

  10. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Patrice Fardellone

    2014-01-01

    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  11. Stepwise nucleosome translocation by RSC remodeling complexes.

    Science.gov (United States)

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-02-19

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome.

  12. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li

    2009-07-01

    Full Text Available Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs, which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  13. Relationship between serum insulin level and age and sex in 980 patients with essential hypertension

    International Nuclear Information System (INIS)

    Objective: To investigate the change of serum insulin level in essential hypertension patients and its relationship with age and sex. Methods: The levels of serum insulin were determined with radioimmunoassay in 980 essential hypertension patients and 120 controls. Results: The levels of serum insulin in the essential hypertension patients were significantly higher than those in the controls (t=4.280, P<0.01). However, there were no significant differences among the levels in different sex and age groups. The same held true for women before and after menopause as well as different stages of hypertension. Conclusion: The average serum insulin level in EH patients was significantly higher than the level in controls, and had positive correlation to mean arterial pressure. But no significant differences were found among different sex and age groups, so serum insulin could be a new independent risk factor of essential hypertension

  14. 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.

  15. Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins

    Science.gov (United States)

    Barallobre-Barreiro, Javier; Oklu, Rahmi; Lynch, Marc; Fava, Marika; Baig, Ferheen; Yin, Xiaoke; Barwari, Temo; Potier, David N.; Albadawi, Hassan; Jahangiri, Marjan; Porter, Karen E.; Watkins, Michael T.; Misra, Sanjay; Stoughton, Julianne; Mayr, Manuel

    2016-01-01

    Aims Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed. Methods and results To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase β1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase β1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins. Conclusion The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis. PMID:27068509

  16. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Dweck Marc R

    2012-07-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR is the gold standard non-invasive method for determining left ventricular (LV mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male with aortic stenosis (aortic valve area 0.93±0.32cm2 were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43 and pattern (P=0.22 of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02. Six patterns of LV adaption were observed: normal ventricular geometry (n=11, concentric remodeling (n=11, asymmetric remodeling (n=11, concentric hypertrophy (n=34, asymmetric hypertrophy (n=14 and LV decompensation (n=10. Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735

  17. Ovarian tumors secreting insulin.

    Science.gov (United States)

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  18. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  19. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  20. Adipokines and Hepatic Insulin Resistance

    OpenAIRE

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarificatio...

  1. Tasting Arterial Blood: What do the Carotid Chemoreceptors Sense?

    Directory of Open Access Journals (Sweden)

    Nanduri R. Prabakhar

    2015-01-01

    Full Text Available The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO-regulated hydrogen sulfide (H2S, stemming from hypoxia, depolarizes type I cells by inhibiting certain K+ channels, facilitates voltage-gated Ca2+ influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signalling is an area of ongoing study.KEY WORDS: Glomus cells, K+ channels, Carbon monoxide, hydrogen sulfide, hypoglycemia, diabetes.

  2. [Abnormal popliteal arteries].

    Science.gov (United States)

    Elbaz, C

    1975-01-01

    Arteriopathy restricted to the popliteal artery, except in cases of atheroma, must indicate three of four unusual diagnoses: the trapped popliteal artery and the dessicating haematoma are anatomo-clinical entities that have been identified only relatively recently. The popliteal artery may be trapped by the medial gastrocnomius muscle, round the tendon of which the artery passes (totally or partially). This results in compression of the artery and eventually in thrombosis. Clinically, intermittent claudication is seen that may deteriorate and lead to gangrene of the toes. Arteriography makes it possible to diagnose the condition as the condition as the artery is considerably displaced inwards. Surgical correction is simple: sectioning of the tendon and repositioning of the artery. Dessicating haematoma of the popliteal artery is due essentially to atheroma, associated with medianecrosis. A "egg-timer" stenosis is found by arteriography and this condition also progresses towards thrombosis. Arterial restoration is called for, usually by bridging. PMID:1230799

  3. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Zhipeng Zeng

    2016-01-01

    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Treg cells have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI. We hypothesize that the interleukin- (IL- 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1 attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  4. On arterial physiology, pathophysiology of vascular compliance, and cardiovascular disease.

    Science.gov (United States)

    Glasser, S P

    2000-01-01

    Traditionally, the main emphasis in hypertension treatment has been on lowering diastolic blood pressure. Recently, this emphasis has been shifting toward systolic blood pressure and pulse pressure, the latter of which might be a better indicator of future clinical events than either blood pressure reading alone or in combination. Increased pulse pressure indicates increased arterial stiffness and hence is commonly seen in older subjects. As patients age and vessels stiffen, there is a resulting loss of arterial compliance, the ability of the vessel to store blood volume temporarily as it is ejected with each systole. The arterial system acts like a Windkessel, or pump, as it converts intermittent flow from the heart into continuous flow to the organs. The process of stiffening occurs via vascular remodeling, a redistribution of the heterogeneous elements of the vascular wall. Endothelial dysfunction can trigger this remodeling process, increasing stiffness, raising blood pressure and pulse pressure, and ultimately leading to atherosclerosis, plaque formation, and attendant clinical events. Because angiotensin-converting enzyme inhibitors and calcium antagonists can restore arterial compliance, they are suitable choices for hypertension treatment when it is complicated by vascular stiffness. PMID:11728285

  5. Cinnamon, glucose and insulin sensitivity

    Science.gov (United States)

    Compounds found in cinnamon not only improve the function of insulin but also function as antioxidants and may be anti-inflammatory. This is very important since insulin function, antioxidant status, and inflammatory response are closely linked; with decreased insulin sensitivity there is also decr...

  6. Differential effects of relaxin deficiency on vascular aging in arteries of male mice.

    Science.gov (United States)

    Jelinic, Maria; Tare, Marianne; Conrad, Kirk P; Parry, Laura J

    2015-08-01

    Exogenous treatment with the naturally occurring peptide relaxin increases arterial compliance and reduces vascular stiffness. In contrast, relaxin deficiency reduces the passive compliance of small renal arteries through geometric and compositional vascular remodeling. The role of endogenous relaxin on passive mechanical wall properties in other vascular beds is unknown. Importantly, no studies have investigated the effects of aging in arteries of relaxin-deficient mice. Therefore, we tested the hypothesis that mesenteric and femoral arteries stiffen with aging, and this is exacerbated with relaxin deficiency. Male wild-type (Rln (+/+)) and relaxin knockout (Rln (-/-)) mice were aged to 3, 6, 12, 18, and 23 months. Passive mechanical wall properties were assessed by pressure myography. In both genotypes, there was a significant increase in circumferential stiffening in mesenteric arteries with aging, whereas in the femoral artery, aging reduced volume compliance. This was associated with a reduced ability of the artery to lengthen with aging. The predominant phenotype observed in Rln (-/-) mice was reduced volume compliance in young mice in both mesenteric and femoral arteries. In summary, aging induces circumferential stiffening in mesenteric arteries and axial stiffening in femoral arteries. Passive mechanical wall properties of Rln (-/-) mouse arteries predominantly differ at younger ages compared with Rln (+/+) mice, suggesting that a lack of endogenous relaxin only has a minor effect on vascular aging.

  7. Clarifying the anatomy of the fifth arch artery

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar Gupta

    2016-01-01

    Full Text Available The artery allegedly forming in the fifth pharyngeal arch has increasingly been implicated as responsible for various vascular malformations in patients with congenitally malformed hearts. Observations from studies on developing embryos, however, have failed to provide support to substantiate several of these inferences such that the very existence of the fifth arch artery remains debatable. To the best of our knowledge, in only a solitary human embryo has a vascular channel been found that truly resembled the artery of the fifth arch. Despite the meager evidence to support its existence, the fifth arch artery has been invoked to explain the morphogenesis of double-barreled aorta, some unusual forms of aortopulmonary communications, and abnormalities of the brachiocephalic arteries. In most of these instances, the interpretations have proved fallible when examined in the light of existing knowledge of cardiac development. In our opinion, there are more plausible alternative explanations for the majority of these descriptions. Double-barreled aorta is more likely to result from retention of the recently identified dorsal collateral channels while abnormalities of brachiocephalic arteries are better explained on the basis of extensive remodeling of aortic arches during fetal development. Some examples of aortopulmonary communications, nonetheless, may well represent persistence of the developing artery of the fifth pharyngeal arch. We here present one such case - a patient with tetralogy of Fallot and pulmonary atresia, in whom the fifth arch artery provided a necessary communication between the ascending aorta and the pulmonary arteries. In this light, we discuss the features we consider to be essential before attaching the tag of "fifth arch artery" to a candidate vascular channel.

  8. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    OpenAIRE

    Sami N. Nasrallah; L. Raymond Reynolds

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism...

  9. New Insulin Delivery Recommendations.

    Science.gov (United States)

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.

  10. Insulin som trickster

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2011-01-01

    grænser nedbrydes i en konstant penetrering af huden, når blodsukkeret måles eller insulinen indsprøjtes. Insulin analyseres som en tricksterfigur, der udøver et grænsearbejde på kroppen, leger med dens kategorier og vender forholdet mellem gift og medicin, frihed og ufrihed, kunstighed og naturlighed...

  11. Insulin gene mutations and diabetes

    OpenAIRE

    Nishi, Masahiro; Nanjo, Kishio

    2011-01-01

    Abstract Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half‐life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four t...

  12. The structural factor of hypertension: large and small artery alterations.

    Science.gov (United States)

    Laurent, Stéphane; Boutouyrie, Pierre

    2015-03-13

    Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.

  13. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow.

    Science.gov (United States)

    Vodstrcil, Lenka A; Tare, Marianne; Novak, Jacqueline; Dragomir, Nicoleta; Ramirez, Rolando J; Wlodek, Mary E; Conrad, Kirk P; Parry, Laura J

    2012-10-01

    Normal pregnancy involves dramatic remodeling of the uterine vasculature, with abnormal vascular adaptations contributing to pregnancy diseases such as preeclampsia. The peptide hormone relaxin is important for the renal and systemic hemodynamic adaptations to pregnancy, and has been shown to increase arterial compliance and outward hypertrophic remodeling. Therefore, we investigated the possibility that relaxin acts on its receptor, RXFP1, to mediate uterine artery compliance in late pregnancy and increase uterine blood flow velocity in rats. RXFP1 was predominantly localized to the tunica media vascular smooth muscle cells in the uterine artery, although receptors were also detected in endothelial cells. Highest expression of Rxfp1 in the uterine artery occurred in estrus and early pregnancy. Isolated uterine arteries from late pregnant rats treated with a monoclonal antibody against circulating relaxin (MCA1) had significantly increased vessel wall stiffness compared with controls, with no reduction in wall thickness. Chronic infusion of relaxin (4 μg/h, osmotic minipump) for 5 d in nonpregnant rats significantly increased uterine artery blood flow velocity. Overall, these data demonstrate a functional role for relaxin in mediating uterine artery compliance in pregnant rats, which may be necessary to maintain adequate uterine blood flow to the uterus and placenta. PMID:22744867

  14. Pregnancy-induced remodeling of heart valves.

    Science.gov (United States)

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

    2015-11-01

    Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves.

  15. Insulin degludec for diabetes mellitus.

    Science.gov (United States)

    2013-07-01

    Over the last few years there has been a steady increase in the number of prescriptions dispensed in primary care for intermediate and long-acting insulin analogues and a reduction in prescriptions for biphasic isophane insulin. For example, in England, the volume of intermediate and long-acting insulin analogues in general practice has risen from approximately 650,000 prescriptions per quarter in 2007 to over 850,000 per quarter in 2012.(1) ▾Insulin degludec (Tresiba, Novo Nordisk) is a new long acting basal insulin analogue for the management of diabetes mellitus in adults.(2) Two strengths of insulin degludec (100 units/mL and 200 units/mL) were launched in the UK in February 2013. Here we discuss evidence for the effectiveness and safety of insulin degludec. PMID:23842634

  16. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    Adipocyte differentiation is tightly controlled by a transcriptional cascade, which directs the extensive reprogramming of gene expression required to convert fibroblast-like precursor cells into mature lipid-laden adipocytes. Recent global analyses of transcription factor binding and chromatin...... remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications....... Such transcription factor hotspots are likely to represent key signaling nodes which integrate multiple adipogenic signals at specific chromatin sites, thereby facilitating coordinated action on gene expression....

  17. CHD chromatin remodelers and the transcription cycle.

    Science.gov (United States)

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  18. Insulin resistance and hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Manuel Romero-Gómez

    2006-01-01

    Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients.Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American.Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin.Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance,steatosis and fibrosis progression.

  19. Platelet Inhibition by Insulin Is Absent in Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Haeften, T.W. van; Akkerman, Jan Willem N.; Heemskerk, J.W.; Gorter, G.; Feijge, M.A.; Mocking, A.I.M.; Ferreira, I.A.

    2006-01-01

    Objective—ADP-induced P2y12 signaling is crucial for formation and stabilization of an arterial thrombus. We demonstrated recently in platelets from healthy subjects that insulin interferes with Ca2+ increases induced by ADP-P2y1 contact through blockade of the G-protein Gi, and thereby with P2y12-m

  20. Combination of Rare Right Arterial Variation with Anomalous Origins of the Vertebral Artery, Aberrant Subclavian Artery and Persistent Trigeminal Artery

    Science.gov (United States)

    Ishihara, H.; San Millán Ruíz, D.; Abdo, G.; Asakura, F.; Yilmaz, H.; Lovblad, K.O.; Rüfenacht, D.A.

    2011-01-01

    Summary A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed. PMID:22005696

  1. On Renal Artery Stenosis

    OpenAIRE

    Eklöf, Hampus

    2005-01-01

    Renal artery stenosis (RAS) is a potentially curable cause of hypertension and azotemia. Besides intra-arterial renal angiography there are several non-invasive techniques utilized to diagnose patients with suspicion of renal artery stenosis. Removing the stenosis by revascularization to restore unobstructed blood flow to the kidney is known to improve and even cure hypertension/azotemia, but is associated with a significant complication rate. To visualize renal arteries with x-ray technique...

  2. Superactive insulin: [B10-aspartic acid]insulin(human)

    International Nuclear Information System (INIS)

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, [Asp/sup B10/] insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [Asp/sup B10/] Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone

  3. Superactive insulin: (B10-aspartic acid)insulin(human)

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, G.P.; Burke, G.T.; Katsoyannis, P.G.

    1987-09-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, (Asp/sup B10/) insulin, corresponding to the mutant proinsulin and evaluated its biological activity. (Asp/sup B10/) Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone.

  4. Application of A Microstructural Constitutive Model of the Pulmonary Artery to Patient-Specific Studies: Validation and Effect of Orthotropy

    OpenAIRE

    Zhang, Yanhang; Dunn, Martin L.; Hunter, Kendall S.; Lanning, Craig; Ivy, D. Dunbar; Claussen, Lori; Chen, S. James; Shandas, Robin

    2007-01-01

    We applied a statistical mechanics based microstructural model of pulmonary artery mechanics, developed from our previous studies of rats with pulmonary arterial hypertension (PAH), to patient-specific clinical studies of children with PAH. Our previous animal studies provoked the hypothesis that increased cross-linking density of the molecular chains may be one biological remodeling mechanism by which the PA stiffens in PAH. This study appears to further confirm this hypothesis since varying...

  5. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

    OpenAIRE

    Goncharova Elena A; Khavin Irene S; Goncharov Dmitry A; Krymskaya Vera P

    2012-01-01

    Abstract Background Increased pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH). The long-acting β2-adrenergic receptor (β2AR) agonist formoterol, a racemate comprised of (R,R)- and (S,S)-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD). PH, a common complication of COPD, increases patients’ morbidity and reduces surviv...

  6. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

    OpenAIRE

    Goncharova, Elena A.; Khavin, Irene S; Goncharov, Dmitry A; Vera P Krymskaya

    2012-01-01

    Background Increased pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH). The long-acting β2-adrenergic receptor (β2AR) agonist formoterol, a racemate comprised of (R,R)- and (S,S)-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD). PH, a common complication of COPD, increases patients’ morbidity and reduces survival. Recen...

  7. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  8. Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in people with Type 1 diabetes

    OpenAIRE

    Ashwell , SG; Stephens, JW; Witthaus, E; Home, PD; Bradley, Clare

    2008-01-01

    OBJECTIVE— The purpose of this study was to compare quality of life and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed with multiple injection regimens. RESEARCH DESIGN AND METHODS— As part of a 32-week, five-center, two-way crossover study in 56 individuals with type 1 diabetes randomized to evening insulin glargine plus mealtime insulin lispro or to NPH insulin (once or twi...

  9. Vertebral artery aneurysms.

    Directory of Open Access Journals (Sweden)

    Ravi Kumar C

    2000-04-01

    Full Text Available Vertebral artery (VA aneurysms are rare. We present our experience with three cases of VA aneurysms. Two aneurysms were located close to the origin of basilar artery while the third patient had a giant posterior inferior cerebellar artery aneurysm. These aneurysms were operated by the far lateral inferior suboccipital approach with good results.

  10. Retinal artery occlusion

    Science.gov (United States)

    ... artery occlusion; Branch retinal artery occlusion; CRAO; BRAO Images Retina References Sanborn GE, Magargal LE. Arterial obstructive disease ... A.M. Editorial team. Related MedlinePlus Health Topics ... audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  11. The reversal of pulmonary vascular remodeling through inhibition of p38 MAPK-alpha: a potential novel anti-inflammatory strategy in pulmonary hypertension

    OpenAIRE

    Church, Alistair C.; Martin, Damien H.; Wadsworth, Roger; Bryson, Gareth; Fisher, Andrew J.; Welsh, David J.; Peacock, Andrew J

    2015-01-01

    The p38 mitogen-activated protein kinase (MAPK) system is increasingly recognized as an important inflammatory pathway in systemic vascular disease but its role in pulmonary vascular disease is unclear. Previous in vitro studies suggest p38 MAPKα is critical in the proliferation of pulmonary artery fibroblasts, an important step in the pathogenesis of pulmonary vascular remodeling (PVremod). In this study the role of the p38 MAPK pathway was investigated in both in vitro and in vivo models of...

  12. Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data

    Science.gov (United States)

    Molthen, Robert C.; Wietholt, Christian; Haworth, Steven T.; Dawson, Christopher A.

    2002-04-01

    In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model.

  13. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Larsen, J J; Mikines, K J;

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration...

  14. Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G kinase-VAMP-3-dependent pathway.

    Science.gov (United States)

    Randriamboavonjy, Voahanginirina; Schrader, Jürgen; Busse, Rudi; Fleming, Ingrid

    2004-02-01

    Insulin-induced vasodilatation is sensitive to nitric oxide (NO) synthase (NOS) inhibitors. However, insulin is unable to relax isolated arteries or to activate endothelial NOS in endothelial cells. Since insulin can enhance platelet endothelial NOS activity, we determined whether insulin-induced vasodilatation can be attributed to a NO-dependent, platelet-mediated process. Insulin failed to relax endothelium-intact rings of porcine coronary artery. The supernatant from insulin-stimulated human platelets induced complete relaxation, which was prevented by preincubation of platelets with a NOS inhibitor, the soluble guanylyl cyclase inhibitor, NS 2028, or the G kinase inhibitor, KT 5823, and was abolished by an adenosine A2A receptor antagonist. Insulin induced the release of adenosine trisphosphate (ATP), adenosine, and serotonin from platelet-dense granules in a NO-dependent manner. This response was not detected using insulin-stimulated platelets from endothelial NOS-/- mice, although a NO donor elicited ATP release. Insulin-induced ATP release from human platelets correlated with the association of syntaxin 2 with the vesicle-associated membrane protein 3 but was not associated with the activation of alphaIIbbeta3 integrin. Thus, insulin elicits the release of vasoactive concentrations of ATP and adenosine from human platelets via a NO-G kinase-dependent signaling cascade. The mechanism of dense granule secretion involves the G kinase-dependent association of syntaxin 2 with vesicle-associated membrane protein 3.

  15. Insulin Induces the Release of Vasodilator Compounds From Platelets by a Nitric Oxide–G Kinase–VAMP-3–dependent Pathway

    Science.gov (United States)

    Randriamboavonjy, Voahanginirina; Schrader, Jürgen; Busse, Rudi; Fleming, Ingrid

    2004-01-01

    Insulin-induced vasodilatation is sensitive to nitric oxide (NO) synthase (NOS) inhibitors. However, insulin is unable to relax isolated arteries or to activate endothelial NOS in endothelial cells. Since insulin can enhance platelet endothelial NOS activity, we determined whether insulin-induced vasodilatation can be attributed to a NO-dependent, platelet-mediated process. Insulin failed to relax endothelium-intact rings of porcine coronary artery. The supernatant from insulin-stimulated human platelets induced complete relaxation, which was prevented by preincubation of platelets with a NOS inhibitor, the soluble guanylyl cyclase inhibitor, NS 2028, or the G kinase inhibitor, KT 5823, and was abolished by an adenosine A2A receptor antagonist. Insulin induced the release of adenosine trisphosphate (ATP), adenosine, and serotonin from platelet-dense granules in a NO-dependent manner. This response was not detected using insulin-stimulated platelets from endothelial NOS−/− mice, although a NO donor elicited ATP release. Insulin-induced ATP release from human platelets correlated with the association of syntaxin 2 with the vesicle-associated membrane protein 3 but was not associated with the activation of αIIbβ3 integrin. Thus, insulin elicits the release of vasoactive concentrations of ATP and adenosine from human platelets via a NO–G kinase–dependent signaling cascade. The mechanism of dense granule secretion involves the G kinase–dependent association of syntaxin 2 with vesicle-associated membrane protein 3. PMID:14744991

  16. ECG manifestations of left ventricular electrical remodeling.

    Science.gov (United States)

    Estes, E Harvey

    2012-01-01

    Research and thinking about the electrocardiographic manifestations of left ventricular hypertrophy has been constrained by a limited conceptual model of the process: heart disease produces chamber enlargement (increased mass), which in turn produces an altered electrocardiogram. The process is much more complex than can be represented in this simple model. A more robust and intricate model is proposed, in which heart (and vascular) disease causes structural changes, electrical changes, biochemical changes, and others, all of which interact to produce electrical remodeling of ventricular myocardium. This electrical remodeling results in a variety of ECG changes. All of these changes interact, leading to an altered clinical course, and to premature death. It is suggested that research, based on this model, can provide new clues to the processes involved, and improve the prediction of clinical outcomes. New directions in research, in recording equipment, and in organizational activities are suggested to test this new model, and to improve the usefulness of the electrocardiogram as a research and diagnostic tool.

  17. Epithelial Cell Apoptosis and Lung Remodeling

    Institute of Scientific and Technical Information of China (English)

    Kazuyoshi Kuwano

    2007-01-01

    Lung epithelium is the primary site of lung damage in various lung diseases. Epithelial cell apoptosis has been considered to be initial event in various lung diseases. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. The other pathway triggered by stresses such as drugs, radiation, infectious agents and reactive oxygen species is mediated by mitochondria. Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis.Epithelial cell death is followed by remodeling processes, which consist of epithelial and fibroblast activation,cytokine production, activation of coagulation pathway, neoangiogenesis, re-epithelialization and fibrosis.Epithelial and mesenchymal interaction plays important roles in these processes. Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases. We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling.

  18. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  19. [Histamine in regulation of bone remodeling processes].

    Science.gov (United States)

    Wiercigroch, Marek; Folwarczna, Joanna

    2013-01-01

    Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H₁ receptor antagonists are widely used in the treatment of allergic conditions, H₂ receptor antagonists in peptic ulcer disease, and betahistine (an H₃ receptor antagonist and H₁ receptor agonist) is used in the treatment of Ménière's disease. Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results. Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H₁ and H₂ receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed. PMID:24018454

  20. Insulin receptor in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-05-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound /sup 125/I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to /sup 125/I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to /sup 125/I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development.

  1. Insulin receptor in Drosophila melanogaster

    International Nuclear Information System (INIS)

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

  2. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  3. Combination BMSC and Niaspan Treatment of Stroke Enhances White Matter Remodeling and Synaptic Protein Expression in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Cynthia Roberts

    2013-11-01

    Full Text Available Objective: White matter remodeling plays an important role in neurological recovery after stroke. Bone marrow stromal cells (BMSCs and Niaspan, an agent which increases high density lipoprotein (HDL, each induces neurorestorative effects and promotes white matter remodeling after stroke in non-diabetic rats. In this study, we test whether combination of BMSCs with Niaspan induces an enhanced white matter remodeling in the ischemic brain of diabetic rats. Research design and methods: Type-1 diabetes (T1DM rats were subjected to transient middle cerebral artery occlusion (MCAo and treated with or without BMSCs; Niaspan; and the combination of BMSCs + Niaspan daily for 14 days after MCAo. Immunostaining for white matter remodeling and synaptic protein expression including NG2; CNPase; BS (Bielschowsky silver; LFB (luxol fast blue; Synaptophysin and SMI-31 immunostaining were performed. Results: BMSC monotherapy did not regulate NG2 and CNPase expression compared to T1DM control rats. Both, combination of BMSCs + Niaspan treatment, and Niaspan monotherapy significantly increase NG2 and CNPase expression compared to T1DM control. While combination BMSC+Niaspan, BMSC monotherapy and Niaspan monotherapy groups all increase BS, LFB, synaptophysin, and SMI-31 expression in the ischemic brain compared to T1DM-MCAo control. In addition, the combination treatment significantly enhances LFB, SMI-31, and Synaptophysin expression compared to BMSC monotherapy. Conclusions: Combination treatment of stroke with BMSCs and Niaspan in T1DM rats increases white matter remodeling and additively increases BMSC monotherapy induced myelination and synaptic plasticity after stroke in T1DM rats.

  4. 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.

  5. Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.

    Science.gov (United States)

    O'brien, S F; Russell, J C; Davidge, S T

    1999-11-01

    We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.

  6. Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Yon Mi; Do, Young Soo; Lee, Moon Kyu; Shin, Sung Wook; Liu, Wei Chiang; Choo; Sung Wook; Choo, In wook [Sungkyunkwan University School of Mecidine, Seoul (Korea, Republic of)

    2003-06-01

    To determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas. Seven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery. Eight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization. Selective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem be helpful in assessing tumor location, but further study is needed.

  7. Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas

    International Nuclear Information System (INIS)

    To determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas. Seven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery. Eight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization. Selective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem be helpful in assessing tumor location, but further study is needed

  8. [Upper extremity arterial diseases].

    Science.gov (United States)

    Becker, F

    2007-02-01

    Compared to lower limb arterial diseases, upper limb arterial diseases look rare, heterogeneous with various etiologies and a rather vague clinical picture, but with a negligible risk of amputation. Almost all types of arterial diseases can be present in the upper limb, but the anatomical and hemodynamic conditions particular to the upper limb often confuse the issue. Thus, atherosclerosis affects mainly the subclavian artery in its proximal segment where the potential of collateral pathway is high making the symptomatic forms not very frequent whereas the prevalence of subclavian artery stenosis or occlusion is relatively high. The clinical examination and the etiologies are discussed according to the clinical, anatomical and hemodynamic context.

  9. The correlations of coronary artery disease with epicardial adipose tissue, insulin resistance and C-reactive protein in different body mass index patients%不同体质量指数人群冠状动脉病变与心外膜脂肪、胰岛素抵抗和C反应蛋白的关系

    Institute of Scientific and Technical Information of China (English)

    王强; 杭涛; 邹莺; 庄微; 程训民; 张启高; 王璟

    2014-01-01

    body mass index(BMl).Methods One hundred and three patients with coronary artery disease were involved in current study who underwent 64-slice dual source CT and percutaneous coronary angiography.Measurements of height,weight,waist circumference (WC) were recorded,and BMI was calculated.All patients were divided into obesity group (n =45) and non-obesity group (n =58) based on BMI.EFV were calculated through 64-slice dual source CT.Blood samples were collected for biochemical examination.Gensini score were adopted to quantify the severity of coronary artery stenosis.The relationship between Gensini score and EFV,CRP and homeostasis model assessment-insulin resistance(HOMA-IR) index were statistical analyzed by SPSS16.0 software.Results The level of CRP,WC,EFV and BMI in obesity group were (11.0 ± 5.8) mg/L,(96.1 ± 7.0) cm,(122.7 ± 43.3) cm3,(27.9 ± 2.9) kg/m2 respectively,significantly higher than those in non-obesity group ((6.5 ± 3.4) mg/L,(86.4 ± 7.6) cm,(92.9 ± 39.5) cm3,(22.4 ± 1.9) kg/m2) and the differences were significant (t =2.24,6.74,3.64,11.74,and P < 0.05).CRP were positively correlated with EFV (r =0.404,0.364,P <0.05) in both obesity and non-obesity group,While HOMA-IR were only associated with BMI in obese group(r =0.322,P <0.05).Gensini score in non-obesity groups were positively related with EFV and CRP (r =0.358,0.315,P < 0.05),while in obesity groups were positively related with EFV,CRP and HOMA-IR(r =0.348,0.297,0.384; P < 0.05).The associations between Gensini score and CRP were not significant in obesity group after adjusting BMI and WC.Multiple linear regression analysis showed that EFV and diabetes mellitus were independent risk factors of patient Gensini score.Conclusion Coronary atherosclerosis is positively related with EFV and CRP in all patients.While,coronary atherosclerosis is influenced by BMI,WC and HOMA-IR in obese group.EFV is an independent risk factor of coronary atherosclerosis.

  10. 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.

  11. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  12. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  13. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  14. Acute occlusion of the left subclavian artery with artery dissection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Subclavian steal syndrome is cerebral or brain stem ischemia resulting from diversion of blood flow from the basilar artery to the subclavian artery, which is caused by occlusive disease of either the subclavian artery or the innominate artery before they branch off at the vertebral artery. In the patients with subclavian steal syndrome the subclavian artery is fed by retrograde flow from the vertebral artery via the carotids and the circle of Willis.

  15. Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    Full Text Available Insulin-like growth factor 1 (IGF-1 and hepatocyte growth factor (HGF are two potent cell survival and regenerative factors in response to myocardial injury (MI. We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01. IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01 and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

  16. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Science.gov (United States)

    Nasrallah, Sami N; Reynolds, L Raymond

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual.4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety.5. PMID:22879797

  17. Extrapancreatic insulin effect of glibenclamide.

    Science.gov (United States)

    Mulder, H; Schopman, W; van der Lely, A J

    1991-01-01

    In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more prolonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide. PMID:1904820

  18. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper;

    2015-01-01

    The structure of insulin, a glucose homeostasis-controlling hormone, is highly conserved in all vertebrates and stabilized by three disulfide bonds. Recently, we designed a novel insulin analogue containing a fourth disulfide bond located between positions A10-B4. The N-terminus of insulin's B......-chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar affinities. Thus...

  19. Insulin Neuroprotection and the Mechanisms

    Institute of Scientific and Technical Information of China (English)

    Li-Yun Yu; Yu Pei

    2015-01-01

    Objective:To analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action.Data Sources:The study is based on the data from PubMed.Study Selection:Articles were selected with the search terms "insulin","blood glucose","neuroprotection","brain","glycogen","cerebral ischemia","neuronal necrosis","glutamate","γ-aminobutyric acid".Results:Insulin has neuroprotection.The mechanisms include the regulation of neurotransmitter,promoting glycogen synthesis,and inhibition of neuronal necrosis and apoptosis.Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia.Conclusions:Intermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6-9 mmol/L.

  20. Phenylacetic acid and arterial vascular properties in patients with chronic kidney disease stage 5 on hemodialysis therapy

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Jankowski, Vera; Henning, Lars;

    2007-01-01

    Phenylacetic acid (PAA) is a recently described uremic toxin that inhibits inducible nitric oxide synthase expression and plasma membrane calcium ATPase and may therefore also be involved in remodeling of arteries. Such vascular effects have not been evaluated yet in patients with chronic kidney ...

  1. Nutritional Modulation of Insulin Resistance

    OpenAIRE

    Weickert, Martin O.

    2012-01-01

    Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss i...

  2. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  3. Cell factories for insulin production

    OpenAIRE

    Baeshen, Nabih A.; Baeshen, Mohammed N; Sheikh, Abdullah; Bora, Roop S; Mohamed Morsi M. Ahmed; Ramadan, Hassan A I; Saini, Kulvinder Singh; Redwan, Elrashdy M.

    2014-01-01

    The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host org...

  4. Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats

    OpenAIRE

    Fu, Jinjuan; Han, Yu; Wang, Hongyong; Wang, Zhen; Liu, Yukai; Chen, Xingjian; Cai, Yue; Guan, Weiwei; Yang, Di; Asico, Laureano D.; ZHOU, Lin; Jose, Pedro A; Zeng, Chunyu

    2014-01-01

    Background Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear. Methods Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory response of isolated mesenteric arteries was evaluated using a small vessel myog...

  5. [Novel immunopathological approaches to pulmonary arterial hypertension].

    Science.gov (United States)

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition. PMID:21536178

  6. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH. PMID:23859515

  7. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

    Full Text Available Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH, the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

  8. Diabetic lipohypertrophy delays insulin absorption.

    Science.gov (United States)

    Young, R J; Hannan, W J; Frier, B M; Steel, J M; Duncan, L J

    1984-01-01

    The effect of lipohypertrophy at injection sites on insulin absorption has been studied in 12 insulin-dependent diabetic patients. The clearance of 125I-insulin from sites with lipohypertrophy was significantly slower than from complementary nonhypertrophied sites (% clearance in 3 h, 43.8 +/- 3.5 +/- SEM) control; 35.3 +/- 3.9 lipohypertrophy, P less than 0.05). The degree of the effect was variable but sufficient in several patients to be of clinical importance. Injection-site lipohypertrophy is another factor that modifies the absorption of subcutaneously injected insulin.

  9. Effects of Perindopril on Left Ventricular Remodeling and Osteopontin Expression in Rats With Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction. Methods In this study male adult SD rats were randomly divided into 3groups: sham-operation group, MI-saline group and MI-perindopril group. Left anterior descending artery was ligated to generate myocardial infarction. Perindopril (2 mg/kg body weight/day) was administered from the next day of MI.Four weeks later, left ventricular diameter (LVEDD and LVESD) and left ventricular ejection fraction was estimated with echocardiography, LVSP, LVEDP and ± dp/dtmax was detected with hemodynamic measurement, cardiomyocyte diameter and interstitial fibrosis infiltration were evaluated with histological methods, and myocardium osteopontin protein expression level was detected with western blot. Results ①Compared with the sham-operation group, all rats with MI developed significant systolic and diastolic dysfunction, as was indicated by decreased LVEF, LVSP and ± dp/dtmax, as well as increased LVEDP. ②Rats with MI showed significantly dilated left ventricles and higher ventricular weight / body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. ③Perindopril treatment partly prevented cardiac dysfunction and left ventricular remodeling as indicated by the parameters mentioned above. ④No osteopontin protein was detected in myocardium of sham-operation rats. In rats with MI, high level osteopontin protein expression was significantly inhibited by perindopril treatment. Conclusions In rats with MI, perindopril treatment significantly prevented left ventricular remodeling and myocardium osteopontin protein expression.

  10. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Directory of Open Access Journals (Sweden)

    Heleen Rienstra

    Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  11. Wnt5a attenuates hypoxia-induced pulmonary arteriolar remodeling and right ventricular hypertrophy in mice.

    Science.gov (United States)

    Jin, Yuling; Wang, Wang; Chai, Sanbao; Liu, Jie; Yang, Ting; Wang, Jun

    2015-12-01

    Hypoxic pulmonary hypertension (HPH), which is characterized by pulmonary arteriolar remodeling and right ventricular hypertrophy, is still a life-threatening disease with the current treatment strategies. The underlying molecular mechanisms of HPH remain unclear. Our previously published study showed that Wnt5a, one of the ligands in the Wnt family, was critically involved in the inhibition of hypoxia-induced pulmonary arterial smooth muscle cell proliferation by downregulation of β-catenin/cyclin D1 in vitro. In this study, we investigated the possible functions and mechanisms of Wnt5a in HPH in vivo. Recombinant mouse Wnt5a (rmWnt5a) or phosphate buffered saline (PBS) was administered to male C57/BL6 mice weekly from the first day to the end of the two or four weeks after exposed to hypoxia (10% O2). Hypoxia-induced pulmonary hypertension was associated with a marked increase in β-catenin/cyclin D1 expression in lungs. Right ventricular systolic pressure and right ventricular hypertrophy index were reduced in animals treated with rmWnt5a compared with PBS. Histology showed less pulmonary vascular remodeling and right ventricular hypertrophy in the group treated with rmWnt5a than with PBS. Treatment with rmWnt5a resulted in a concomitant reduction in β-catenin/cyclin D1 levels in lungs. These data demonstrate that Wnt5a exerts its beneficial effects on HPH by regulating pulmonary vascular remodeling and right ventricular hypertrophy in a manner that is associated with reduction in β-catenin/cyclin D1 signaling. A therapy targeting the β-catenin/cyclin D1 signaling pathway might be a potential strategy for HPH treatment.

  12. Effect of hepatocyte growth factor on left ventricular remodeling after acute myocardial infarction in canine

    Institute of Scientific and Technical Information of China (English)

    Ping LI; Tingshu YANG; Liling LIANG

    2006-01-01

    Background and objectives To investigate the effect of hepatocyte growth factor (HGF) on left ventricular (LV) remodeling after acute myocardial infarction (AMI). Methods AMI was produced by ligation of proximal left anterior descending coronary artery(LAD) in 12 mongrel canines. These animals were randomized into 2 groups. In HGF group (n=6), canines were injected with pcDNA3-HGF lml (about 300ug) at the margin of infarcted myocardium; in control group (n=6) canines were injected with equal volume of normal saline. Cardiac function and left ventricular remodeling were evaluated with echocardiography at 1, 4, 8 weeks after MI. LV myocardium specimens were obtained at 8 weeks and stained with hematoxylin and eosin for histological examination or with sirius red to assess the collagen content. Results Compared with control group, LVEF in HGF group was significantly higher at 4 weeks (49.61+6.66 vs 39.84+6.39; P<0.05) and at 8 weeks (51.57+8.53 vs 40.61+7.67; P<0.05) after AMI, while LVESV was significantly lower in HGF group than that in control group at 8 weeks after AMI (18.98+3.47 vs 25.66+5.86; P<0.05). Posterior left ventricular wall thickness decreased significantly from 1 wk to 8 wks after AMI in control group, while remained unchanged in HGF group. Compared with control group, histological examination showed more neovascularization and less scar, and sirius red staining indicated higher volume of type Ⅲ collagen (7.10±4.06% vs 3.77±1.09%; P<0.05) and lower collagen Ⅰ/Ⅲ ratio value (1.11±0.52 vs 2.94±2.48; P<0.05)in HGF group. Conclusion HGF gene transfer might improve cardiac function and LV remodeling after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis, and reducing myocardial scarring.

  13. Renovascular hypertension causes cerebral vascular remodeling

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Xiangpen Li; Yi Li; Qingyu Shen; Xiaoming Rong; Ruxun Huang; Ying Peng

    2011-01-01

    Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

  14. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  15. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    Science.gov (United States)

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

  16. Biomechanical Remodeling of the Diabetic Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Liao, Donghua; Yang, Jian;

    2010-01-01

    in diabetes mellitus is complex in nature, multi-factorial (motor dysfunction, autonomic neuropathy, glycemic control, psychological factors, etc.) and is not well understood. Histologically, many studies have demonstrated prominent proliferation of different GI wall layers during diabetes. During the past......Gastrointestinal tract sensory-motor abnormalities are common in patients with diabetes mellitus with symptoms arising from the whole GI tract. Common complaints include dysphasia, early satiety, reflux, constipation, abdominal pain, nausea, vomiting, and diarrhea. The pathogenesis of GI symptoms...... several years, several studies demonstrated that experimental diabetes induces GI morphological and biomechanical remodeling. Following the development of diabetes, the GI wall becomes thicker and the stiffness of the GI wall increases in a time-dependent manner. It is well known that mechanosensitive...

  17. Bilateral accessory thoracodorsal artery.

    Science.gov (United States)

    Natsis, Konstantinos; Totlis, Trifon; Tsikaras, Prokopios; Skandalakis, Panagiotis

    2006-09-01

    The subscapular artery arises from the third part of the axillary artery and gives off the circumflex scapular and the thoracodorsal arteries. Although anatomical variations of the axillary artery are very common, the existence of a unilateral accessory thoracodorsal artery has been described in the literature only once. There are no reports of bilateral accessory thoracodorsal artery, in the literature. In the present study, a bilateral accessory thoracodorsal artery, originating on either side of the third part of the axillary artery, is described in a 68-year-old female cadaver. All the other branches of the axillary artery had a typical origin, course, distribution and termination. This extremely rare anatomical variation apart from the anatomical importance also has clinical significance for surgeons in this area. Especially, during the dissection or mobilization of the latissimus dorsi that is partly used for coverage problems in many regions of the body and also in dynamic cardiomyoplasty, any iatrogenic injury of this accessory artery may result in ischemia and functional loss of the graft.

  18. PNPLA3 mediates hepatocyte triacylglycerol remodeling.

    Science.gov (United States)

    Ruhanen, Hanna; Perttilä, Julia; Hölttä-Vuori, Maarit; Zhou, You; Yki-Järvinen, Hannele; Ikonen, Elina; Käkelä, Reijo; Olkkonen, Vesa M

    2014-04-01

    The I148M substitution in patatin-like phospholipase domain containing 3 (PNPLA3(I148M)) determines a genetic form of nonalcoholic fatty liver disease. To elucidate the mode of PNPLA3 action in human hepatocytes, we studied effects of WT PNPLA3 (PNPLA3(WT)) and PNPLA3(I148M) on HuH7 cell lipidome after [(13)C]glycerol labeling, cellular turnover of oleic acid labeled with 17 deuterium atoms ([D17]oleic acid) in triacylglycerols (TAGs), and subcellular distribution of the protein variants. PNPLA3(I148M) induced a net accumulation of unlabeled TAGs, but not newly synthesized total [(13)C]TAGs. Principal component analysis (PCA) revealed that both PNPLA3(WT) and PNPLA3(I148M) induced a relative enrichment of TAGs with saturated FAs or MUFAs, with concurrent enrichment of polyunsaturated phosphatidylcholines. PNPLA3(WT) associated in PCA with newly synthesized [(13)C]TAGs, particularly 52:1 and 50:1, while PNPLA3(I148M) associated with similar preexisting TAGs. PNPLA3(WT) overexpression resulted in increased [D17]oleic acid labeling of TAGs during 24 h, and after longer incubations their turnover was accelerated, effects not detected with PNPLA3(I148M). PNPLA3(I148M) localized more extensively to lipid droplets (LDs) than PNPLA3(WT), suggesting that the substitution alters distribution of PNPLA3 between LDs and endoplasmic reticulum/cytosol. This study reveals a function of PNPLA3 in FA-selective TAG remodeling, resulting in increased TAG saturation. A defect in TAG remodeling activity likely contributes to the TAG accumulation observed in cells expressing PNPLA3(I148M). PMID:24511104

  19. Arterial pulse wave velocity, inflammatory markers, pathological GH and IGF states, cardiovascular and cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Michael R Graham

    2008-12-01

    Full Text Available Michael R Graham1, Peter Evans2, Bruce Davies1, Julien S Baker11Health and Exercise Science Research Unit, Faculty of Health Sport and Science, University of Glamorgan, Pontypridd, Wales, United Kingdom; 2Royal Gwent Hospital, Newport, Gwent, United KingdomAbstract: Blood pressure (BP measurements provide information regarding risk factors associated with cardiovascular disease, but only in a specific artery. Arterial stiffness (AS can be determined by measurement of arterial pulse wave velocity (APWV. Separate from any role as a surrogate marker, AS is an important determinant of pulse pressure, left ventricular function and coronary artery perfusion pressure. Proximal elastic arteries and peripheral muscular arteries respond differently to aging and to medication. Endogenous human growth hormone (hGH, secreted by the anterior pituitary, peaks during early adulthood, declining at 14% per decade. Levels of insulin-like growth factor-I (IGF-I are at their peak during late adolescence and decline throughout adulthood, mirror imaging GH. Arterial endothelial dysfunction, an accepted cause of increased APWV in GH deficiency (GHD is reversed by recombinant human (rh GH therapy, favorably influencing the risk for atherogenesis. APWV is a noninvasive method for measuring atherosclerotic and hypertensive vascular changes increases with age and atherosclerosis leading to increased systolic blood pressure and increased left ventricular hypertrophy. Aerobic exercise training increases arterial compliance and reduces systolic blood pressure. Whole body arterial compliance is lowered in strength-trained individuals. Homocysteine and C-reactive protein are two infl ammatory markers directly linked with arterial endothelial dysfunction. Reviews of GH in the somatopause have not been favorable and side effects of treatment have marred its use except in classical GHD. Is it possible that we should be assessing the combined effects of therapy with rhGH and rh

  20. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.

    Science.gov (United States)

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling.

  1. Effects of losartan on ventricular remodeling in experimental infarction in rats

    Directory of Open Access Journals (Sweden)

    Zornoff Leonardo A. M.

    2000-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of losartan on ventricular remodeling and on survival after myocardial infarction in rats. METHODS: After surgical occlusion of left coronary artery, 84 surviving male Wistar rats were divided into two groups: LO treated with losartan (20mg/kg/day, n=33 and NT (n=51, without medication. After 3 months, we analyzed mortality; ventricular to body mass ratio (VM /BM; myocardial hydroxyproline concentration (HOP; isovolumetric pressure, +dp/dt, -dp/dt, and diastolic volume/left ventricle mass ratio (VO/LV. RESULTS: Mortality was: LO = 22%, and NT = 47% (p0.05. The V0/LV values (median were 0.24 mL/g in group LO and 0.31 mL/g in group NT (p<0.05 compared to NT group. There were no differences between the groups for +dp/dt and -dp/dt parameters. CONCLUSION: 1- The use of losartan myocardial infarction causes an attenuation of ventricular remodeling, bringing about an increased survival, an attenuation of ventricular hypertrophy and dilation, and an improvement of the isovolumetric pressure; 2- the treatment does not modify the myocardial collagen concentration.

  2. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

    2013-08-15

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

  3. Effect of carvedilol on cardiac function and left ventricular remodeling in rats after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    张军; 贾国良; 王海昌

    2003-01-01

    Objective: To observe the effect of carvedilol injection on left ventricular function and collagen remodeling in rat with myocardial infarction. Methods: Sixty rats with a model of myocardial infarction were randomly divided into nine groups. The rats of therapeutical group were treated with carvedilol injection (2 mg/d intraperitoneal injection) and/or captopil (2 g/L drinking water). Acute myocardial infarction (AMI) group did not receive drug treatment. The animals were sacrificed at 4 weeks and 8 weeks after coronary artery ligation. The levels of plasma angiotensin Ⅱ and plasma aldosterone and left ventricle function were determined at different time. The collagen content and the ratio of type I and Ⅲ collagen of noninfarcted area were also assessed. Results: Compared with AMI group, the levels of plasma and myocardium angiotensin Ⅱ and plasma aldosterone in both carvedilol and captopil group decreased at the eighth week (P<0.05). In addition, carvedilol improved systolic and diastolic function (P<0.05). Compared with sham group, both collagen content and the ratio of type Ⅰ/Ⅲ collagen of noninfarcted area increased in AMI4 and AMI8 group (P<0.05). The hydroxyproline levels and the ratio of type Ⅰ/Ⅲ collagen significantly decreased after carvedilol and/or captopil treatment , compared with AMI group at 4 or 8 week (P<0.05). Conclusion: Carvedilol can improve cardiac function after myocardial infarction and has beneficial effect on left ventricular remodeling.

  4. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    International Nuclear Information System (INIS)

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

  5. Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T;

    2012-01-01

    BACKGROUND: Endothelin-1 (ET1) is a potent vasoconstrictor peptide with pro-mitogenic and pro-inflammatory properties and is therefore of interest in the development of endothelial dysfunction, endothelium-dependent flow-related remodeling, and hypertension-related remodeling. ET1 can be formed...... through cleavage of big ET1 by endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). METHOD: We investigated whether the dual NEP/ECE inhibitor SOL1 improves resistance artery function and structure in 12 weeks old spontaneously hypertensive rats (SHRs) and whether arterial structural...

  6. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  7. Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors.

    OpenAIRE

    Keefer, L M; Piron, M A; DE MEYTS, P.

    1981-01-01

    Human insulin synthesized from A and B chains separately produced in Escherichia coli from cloned synthetic genes (prepared by the Eli Lilly Research Laboratories, Indianapolis, IN) was characterized by examining its interaction with human cultured lymphocytes, human circulating erythrocytes in vitro, and isolated rat fat cells. The binding behavior of the biosynthetic insulin with human cells was indistinguishable from that of native human or porcine insulins, with respect to affinity, assoc...

  8. Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

    Science.gov (United States)

    Zeng, Yi; Zhang, Le; Hu, Zhiping

    2016-01-01

    Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

  9. Angioplasty and stent placement - peripheral arteries - discharge

    Science.gov (United States)

    Percutaneous transluminal angioplasty - peripheral artery - discharge; PTA - peripheral artery - discharge; Angioplasty - peripheral artery - discharge; Balloon angioplasty - peripheral artery- discharge; PAD - PTA ...

  10. Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation.

    Science.gov (United States)

    Keen, Adam N; Shiels, Holly A; Crossley, Dane A

    2016-07-01

    Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in

  11. Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

    OpenAIRE

    Roth, R A; Cassell, D J; Wong, K. Y.; Maddux, B A; Goldfine, I D

    1982-01-01

    Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding...

  12. Effect of Cocaine on Pulmonary Vascular Remodeling and Hemodynamics in Human Immunodeficiency Virus-Transgenic Rats.

    Science.gov (United States)

    Dalvi, Pranjali; Spikes, Leslie; Allen, Julie; Gupta, Vijayalaxmi G; Sharma, Himanshu; Gillcrist, Marion; Montes de Oca, Jamison; O'Brien-Ladner, Amy; Dhillon, Navneet K

    2016-08-01

    Human immunodeficiency virus (HIV)-related pulmonary arterial hypertension has been found to be more prevalent in intravenous drug users. Our earlier cell-culture findings reported down-regulation of bone morphogenetic protein receptors (BMPRs) in combination with enhanced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) in the presence of HIV-Trans-activator of transcription (Tat) and cocaine compared with either treatment alone. Here, we report physiologic evidence of significant increases in mean pulmonary arterial pressure in HIV-transgenic (Tg) rats intraperitoneally administered 40 mg/kg body weight cocaine (HIV-cocaine group) once daily for 21 days when compared with HIV-Tg rats given saline (HIV group) or wild-type (WT) Fischer 334 rats treated with (WT-cocaine group) and without cocaine (WT group). In addition, right ventricle systolic pressure was also found to be significantly higher in the HIV-cocaine rats compared with the WT group. Significant down-regulation in protein expression of BMPR-2 and BMPR-1B was observed in total lung extract from HIV-cocaine rats compared with the other three groups. Furthermore, the PASMCs isolated from HIV-cocaine rats demonstrated a higher level of proliferation and lower levels of apoptosis compared with cells isolated from other rat groups. Interestingly, corroborating our earlier cell-culture findings, we observed higher expression of BMPR-2 and BMPR-1B messenger RNA and significantly lower levels of BMPR-2 and BMPR-1B protein in HIV-cocaine PASMCs compared with cells isolated from all other groups. In conclusion, our findings support an additive effect of cocaine and HIV on smooth muscle dysfunction, resulting in enhanced pulmonary vascular remodeling with associated elevation of mean pulmonary arterial pressure and right ventricle systolic pressure in HIV-Tg rats exposed to cocaine. PMID:26820592

  13. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  14. Hemodynamic Change and Liver Remodeling%血流动力学改变与肝脏重塑

    Institute of Scientific and Technical Information of China (English)

    李翠翠; 叶啟发

    2016-01-01

    肝切除、肝静脉血栓形成、肝动脉栓塞、肝移植、门静脉高压等各种情况下肝脏出现巨大的血流变化.为了降低门静脉高压导致的门静脉流量减少,肝动脉缓冲区做出反应以增加肝动脉流量.与增加的肝动脉流量相关的血流动力学压力促进巨噬细胞浸润,调节门静脉肌成纤维细胞功能,有助于门静脉高压下汇管区纤维化的发展.外泌体源性microRNAs参与了肝脏重塑的过程,它可能是一个潜在的治疗靶点.本文就肝脏血流动力学变化导致肝脏重塑的相关机制作一综述.%Dynamic blood flow changes occur in the liver in various conditions,such as liver resection,hepatic vein thrombosis,hepatic artery embolization,liver transplantation and portal hypertension.In portal hypertension,the hepatic arterial buffer response increases hepatic arterial flow in response to decreased portal venous flow in portal hypertension.Hemodynamic stresses associated with increased hepatic arterial flow promote infiltration of macrophages that modulate function of portal myofibroblast and contribute to the development of portal tract fibrosis in portal hypertension.Exosomes derived microRNAs are involved in mechanisms of liver remodeling,and hence they can be a potential therapeutic tool.The related mechanisms of hepatic hemodynamic changes in liver remodeling was reviewed in this paper.

  15. In vivo characterization of insulin uptake by dog renal cortical epithelium

    International Nuclear Information System (INIS)

    In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: [3H]dextran greater than 70 kDa (plasma reference), [14C]inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below [14C]inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching [14C]inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM

  16. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  17. Popliteal artery entrapment syndrome.

    LENUS (Irish Health Repository)

    O'Leary, D P

    2010-01-01

    Popliteal artery entrapment syndrome is a rare abnormality of the anatomical relationship between the popliteal artery and adjacent muscles or fibrous bands in the popliteal fossa. The following is a case report of a 19 year old female, in whom popliteal artery entrapment syndrome was diagnosed, and successfully treated surgically. A review of literature is also presented and provides details on how PAES is classified, diagnosed both clinically and radiologically, and treated surgically.

  18. [Popliteal artery entrapment syndrome].

    Science.gov (United States)

    Musumeci, S; Iuppa, A; Beneventano, G; Rinella, P; Mammano, M; Cinquegrani, E

    1986-12-15

    Trapped popliteal artery syndrome is relatively uncommon: the literature reports some 60 cases. The clinical picture is linked to compression of the popliteal artery by the gastrocnemius as it contracts, thus distorting the arterial route. The result is an interruption in the blood flow distally to the area involved due to stenosis of the blood vessel that is at first functional but becomes organic. PMID:3808379

  19. Celiac Artery Compression Syndrome

    Directory of Open Access Journals (Sweden)

    Mohammed Muqeetadnan

    2013-01-01

    Full Text Available Celiac artery compression syndrome is a rare disorder characterized by episodic abdominal pain and weight loss. It is the result of external compression of celiac artery by the median arcuate ligament. We present a case of celiac artery compression syndrome in a 57-year-old male with severe postprandial abdominal pain and 30-pound weight loss. The patient eventually responded well to surgical division of the median arcuate ligament by laparoscopy.

  20. [Medication of the month. Insulin glargine (Lantus)].

    Science.gov (United States)

    Scheen, A J

    2004-02-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy. PMID:15112902

  1. Carotid body, insulin and metabolic diseases: unravelling the links

    Directory of Open Access Journals (Sweden)

    Silvia V Conde

    2014-10-01

    Full Text Available The carotid bodies (CB are peripheral chemoreceptors that sense changes in arterial blood O2, CO2 and pH levels. Hypoxia, hypercapnia and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN. CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnoea (OSA is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.

  2. Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology.

    Science.gov (United States)

    Godsland, Ian F; Johnston, Desmond G

    2008-09-01

    Clustering of risk factors for coronary heart disease and diabetes is well established, particularly in relation to insulin resistance. To determine whether evaluation of risk factor clustering will contribute to risk assessment, it is first necessary to discriminate co-association between risk factors from correlation. We undertook this in a large homogenous group, using a sophisticated measure of insulin sensitivity and a broad range of risk factors. Cross-sectional analysis of an occupational cohort using regression and factor analyses was performed. Subjects were 472 apparently healthy white men. The main outcome measures were insulin sensitivity, S(I), by minimal model analysis of the intravenous glucose tolerance test plus liver function and hematologic variables, including the inflammation indices, leukocyte count, and erythrocyte sedimentation rate. The S(I) correlated independently with serum gamma-glutamyl transferase (GGT), aspartate transaminase, and alkaline phosphatase activities; blood pressure; leukocyte count; and erythrocyte sedimentation rate (P GGT activity (loadings >0.40). Mean arterial pressure was not a feature (loading 0.29), neither were indices of subclinical inflammation. In apparently healthy men, blood pressure and indices of subclinical inflammation do not cluster with other insulin resistance-related risk factors, despite correlating with insulin sensitivity. In contrast, both GGT activity and uric acid concentrations correlated with insulin sensitivity and co-associated with insulin resistance-related risk factors and are therefore components of a true risk factor cluster. PMID:18702943

  3. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  4. Heritability of cilioretinal arteries

    DEFF Research Database (Denmark)

    Taarnhøj, Nina Charlotte; Munch, Inger C; Kyvik, Kirsten O;

    2005-01-01

    of healthy monozygotic and dizygotic twins were examined using digital fundus photography and visual assessment of grayscale fundus photographs and color transparencies to detect the presence of cilioretinal arteries. RESULTS: Cilioretinal arteries were present in 45.1% of participants and 28.8% of eyes....... The majority of cilioretinal arteries, 88.2%, were located temporally, and 11.8% were located nasally. Monozygotic twins had higher concordance rates for cilioretinal arteries than dizygotic twins. Tetrachoric correlations and Mantel-Haenszel odds ratios demonstrated statistically significant evidence...

  5. Peripheral artery disease - legs

    Science.gov (United States)

    ... if they have a history of: Abnormal cholesterol Diabetes Heart disease (coronary artery disease) High blood pressure ( hypertension ) Kidney disease involving hemodialysis Smoking Stroke ( cerebrovascular disease )

  6. [Local lipohypertrophy in insulin treatment].

    Science.gov (United States)

    Herold, D A; Albrecht, G

    1993-01-01

    Local lipoatrophy and lipohypertrophy at injection sites are well known side effects of treatment with insulin. Conditions favouring these local complications are created when repeated or continuous injections are given into the same areas. We report on a 27-year-old female patient who suffered from persistent local swellings after use of an external pump which continuously injected human insulin via indwelling cannulas.

  7. Extrapancreatic insulin effect of glibenclamide

    NARCIS (Netherlands)

    H.W. Mulder (H. W.); W. Schopman Sr. (W.); A-J. van der Lely (Aart-Jan)

    1991-01-01

    textabstractIn eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The r

  8. Obesity and insulin resistance in resistant hypertension: implications for the kidney.

    Science.gov (United States)

    Rao, Akhilesh; Pandya, Vishwam; Whaley-Connell, Adam

    2015-05-01

    There is recognition that the obesity epidemic contributes substantially to the increasing incidence of CKD and resistant hypertension (HTN). The mechanisms by which obesity promotes resistance are an area of active interest and intense investigation. It is thought that increases in visceral adiposity lead to a proinflammatory, pro-oxidative milieu that promote resistance to the metabolic actions of insulin. This resistance to insulin at the level of skeletal muscle tissue impairs glucose disposal/utilization through actions on the endothelium that include vascular rarefaction, reductions in vascular relaxation, and vascular remodeling. Insulin resistance derived from increased adipose tissue and obesity has system-wide implications for other tissue beds such as the kidney that affects blood pressure regulation. The additional autocrine and paracrine activities of adipose tissue contribute to inappropriate activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system that promote kidney microvascular remodeling, stiffness, and sodium (Na(+)) retention that in turn promote HTN and in the CKD patient, resistance. In this review, we will summarize the important mechanisms that link obesity to CKD as they relate to resistant HTN.

  9. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels;

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is...... lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on...

  10. Right Coronary Artery Arising from Circumflex Artery: A Case of Single Coronary Artery Anomaly

    Directory of Open Access Journals (Sweden)

    Hekim Karapınar

    2013-08-01

    Full Text Available Coronary artery anomalies could be cause of conflicts for catheterization, especially, in the setting of acute coronary syndrome. We described a case of rare single coronary anomaly which the right coronary artery arisen from terminal part of left circumflex artery. Patient was presented with non-ST segment elevation myocardial infarction. Coronary angiography revealed subtotal stenosis of left anterior descending artery at the mid portion. Left circumflex artery lying in usual route and branch out the posterior descending artery. The right coronary artery arisen from terminal circumflex artery. Left anterior descending artery lesion was stented without any complication.

  11. Coronary artery bypass surgery in the diabetic patient.

    LENUS (Irish Health Repository)

    Maher, M

    2012-02-03

    Coronary artery and peripheral occlusive arterial disease frequently complicate diabetes mellitus, with death due to atherosclerotic coronary artery disease being three times more likely in diabetic compared to non-diabetic patients. The profile of 32 diabetic patients and 32 matched controls who underwent coronary artery bypass (CABG) is studied and their early and late postoperative outcomes are described. The mean age was 61 +\\/- 1 year in both groups. The diabetic group comprised 26 non-insulin dependent and 6 insulin dependent diabetics, who had a mean duration of diabetes of 8.5 years (range 2 months--35 years). The median number of grafts per patient performed in the diabetic group and the control group was 3.5 and 3 respectively. There was no mortality in the series, however considerably greater wound morbidity rates were encountered in the diabetic group when compared to matched controls. One renal transplant patient in the diabetic group suffered irreversible acute tubular necrosis and became dialysis dependent post-operatively. Longterm follow-up showed no longterm mortality in either group, with full relief of angina achieved in 75% of diabetic patients compared with 87.5% of matched controls. In addition diabetic patients suffered greater longterm cardiac morbidity than the control group (21.8% versus 12.5%). The results of this study suggest that CABG is a safe operation for the diabetic patient. Diabetic patients receive satisfactory symptomatic relief of angina, but suffer increased perioperative wound complications and greater incidence of longterm cardiac morbidity.

  12. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  13. INSULIN RESISTANCE AND CAROTID ATHEROSCLEROSIS IN 221 PATIENTS WITH POTENTIAL HYPERGLYCEMIA

    Institute of Scientific and Technical Information of China (English)

    Bo Yang; Tian-de Li; Jin-song Wang; Guang Zhi; Wen-sheng Jin; Yong Xu

    2005-01-01

    Objective To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia.Methods A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR).Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed.Results With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and In(HOMA-IR) were related to IMT, hence were risk factors for IMT increase.Conchsion Insulin resistance is implicated in atherogenesis.

  14. Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension.

    Science.gov (United States)

    Belo, V A; Guimarães, Danielle A; Castro, Michele Mazzaron

    2015-01-01

    For vascular remodeling in hypertension, it is essential that vascular smooth muscle cells (VSMCs) reshape in order to proliferate and migrate. The extracellular matrix (ECM) needs to be degraded to favor VSMC migration. Many proteases, including matrix metalloproteinases (MMPs), contribute to ECM proteolysis and VSMC migration. Bioactive peptides, hemodynamic forces and reactive oxygen-nitrogen species regulate MMP-2 expression and activity. Increased MMP-2 activity contributes to hypertension-induced maladaptive arterial changes and sustained hypertension. New ECM is synthesized to supply VSMCs with bioactive mediators, which stimulate hypertrophy. MMP-2 stimulates the interaction of VSMCs with newly formed ECM, which triggers intracellular signaling via integrins to induce a phenotypic switch and persistent migration. VSMCs switch from a contractile to a synthetic phenotype in order to migrate and contribute to vascular remodeling in hypertension. MMPs also disrupt growth factors bound to ECM, thus contributing to their capacity to regulate VSMC migration. This review sheds light on the proteolytic effects of MMP-2 on ECM and non-ECM substrates in the vasculature and how these effects contribute to VSMC migration in hypertension. The inhibition of MMP activity as a therapeutic target may make it possible to reduce arterial maladaptation caused by hypertension and prevent the resulting fatal cardiovascular events. PMID:26731549

  15. Effects of Buyang Huanwu Decoction on Ventricular Remodeling and Differential Protein Profile in a Rat Model of Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Ying Chun Zhou

    2012-01-01

    Full Text Available Buyang Huanwu decoction (BYHWD is a well-known and canonical Chinese medicine formula from “Correction on Errors in Medical Classics” in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD artery ligation in rats. BYHWD treatment (18 g/kg/day decreased heart weight/body weight (HW/BW, left ventricle (LV dimension at end diastole (LVDd and increased LV ejection fraction (LVEF and LV fractional shortening (LVFS significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF was downregulated; heat shock protein beta-6 (HSPB6 and peroxiredoxin-6 (PRDX6 were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF.

  16. Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.

    Science.gov (United States)

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

  17. Impaired glutathione redox system paradoxically suppresses angiotensin II-induced vascular remodeling.

    Directory of Open Access Journals (Sweden)

    Kazuma Izawa

    Full Text Available BACKGROUND: Angiotensin II (AII plays a central role in vascular remodeling via oxidative stress. However, the interaction between AII and reduced glutathione (GSH redox status in cardiovascular remodeling remains unknown. METHODS: In vivo: The cuff-induced vascular injury model was applied to Sprague Dawley rats. Then we administered saline or a GSH inhibitor, buthionine sulfoximine (BSO, 30 mmol/L in drinking water for a week, subsequently administered 4 more weeks by osmotic pump with saline or AII (200 ng/kg/minute to the rats. In vitro: Incorporation of bromodeoxyuridine (BrdU was measured to determine DNA synthesis in cultured rat vascular smooth muscle cells (VSMCs. RESULTS: BSO reduced whole blood GSH levels. Systolic blood pressure was increased up to 215 ± 4 mmHg by AII at 4 weeks (p<0.01, which was not affected by BSO. Superoxide production in vascular wall was increased by AII and BSO alone, and was markedly enhanced by AII+BSO. The left ventricular weight to body weight ratio was significantly increased in AII and AII+BSO as compared to controls (2.52 ± 0.08, 2.50 ± 0.09 and 2.10 ± 0.07 mg/g respectively, p<0.05. Surprisingly, the co-treatment of BSO totally abolished these morphological changes. Although the vascular circumferential wall stress was well compensated in AII, significantly increased in AII+BSO. The anti-single-stranded DNA staining revealed increasing apoptotic cells in the neointima of injured arteries in BSO groups. BrdU incorporation in cultured VSMCs with AII was increased dose-dependently. Furthermore it was totally abolished by BSO and was reversed by GSH monoethyl ester. CONCLUSIONS: We demonstrated that a vast oxidative stress in impaired GSH redox system totally abolished AII-induced vascular, not cardiac remodeling via enhancement of apoptosis in the neointima and suppression of cell growth in the media. The drastic suppression of remodeling may result in fragile vasculature intolerable to mechanical

  18. [Efficacy of metformin as initial therapy in patients with coronary artery disease and diabetes type 2].

    Science.gov (United States)

    Lavrenko, A V; Kutsenko, L A; Solokhina, I L; Rasin, M S; Kaĭdashev, I P

    2011-01-01

    The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha). Reduced activity of systemic inflammation had a beneficial effect on the course of coronary artery disease (significant decrease in the functional class of stable angina). Type 2 diabetes appears to be quite successfully modifiable risk factor for coronary artery disease by the adequate controls.

  19. Artery Agenesis: Ipsilateral Common Carotid Artery Hypoplasia

    Directory of Open Access Journals (Sweden)

    Omer Kaya

    2014-01-01

    Full Text Available A 42-year-old female patient, who had been diagnosed with an occlusion of her left internal carotid artery (ICA following Doppler ultrasonographic (US and digitally-subtracted angiographic (DSA examinations performed in an outer healthcare center in order to eliminate the underlying cause of her complaint of amorosis fugax, later applied to our hospital with the same complaint. At Doppler US performed in our hospital’s radiology department, her right common carotid artery (CCA was normal, but her left CCA was hypoplastic. The right internal artery (ICA was validated as normal. At the left side, however, the ICA was apparent only as a stump and it did not demonstrate a continuity. The diagnosis of ICA agenesis was confirmed by the utilization of Doppler US, CT, and DSA imaging, and it was concluded also that ipsilateral CCA hypoplasia could be evaluated as an important clue to the diagnosis of ICA agenesis.

  20. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  1. Diagnosis of Intracranial Artery Dissection

    Science.gov (United States)

    KANOTO, Masafumi; HOSOYA, Takaaki

    2016-01-01

    Cerebral arterial dissection is defined as a hematoma in the wall of a cervical or an intracranial artery. Cerebral arterial dissection causes arterial stenosis, occlusion, and aneurysm, resulting in acute infarction and hemorrhage. Image analysis by such methods as conventional angiography, computed tomography, magnetic resonance imaging, and so on plays an important role in diagnosing cerebral arterial dissection. In this study, we explore the methods and findings involved in the diagnosis of cerebral arterial dissection. PMID:27180630

  2. Remodeling of alveolar septa after murine pneumonectomy.

    Science.gov (United States)

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  3. Cutaneous remodeling and photorejuvenation using radiofrequency devices

    Directory of Open Access Journals (Sweden)

    Elsaie Mohamed

    2009-01-01

    Full Text Available Radio frequency (RF is electromagnetic radiation in the frequency range of 3-300GHz. The primary effects of RF energy on living tissue are considered to be thermal. The goal of the new devices based on these frequency ranges is to heat specific layers of the skin. The directed use of RF can induce dermal heating and cause collagen degeneration. Wound healing mechanisms promote the remodeling of collagen and wound contraction, which ultimately clinically enhances the appearance of mild to moderate skin laxity. Preliminary studies have reported efficacy in the treatment of laxity that involves the periorbital area and jowls. Because RF energy is not dependent on specific chromophore interaction, epidermal melanin is not at risk of destruction and treatment of all skin types is possible. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision and treatment of unwanted hair, vascular lesions and inflammatory acne. The use of RF is becoming more popular, although a misunderstanding exists regarding the mechanisms and limitations of its actions. This concise review serves as an introduction and guide to many aspects of RF in the non ablative rejuvenation of skin.

  4. Reconstitutions of mitochondrial inner membrane remodeling.

    Science.gov (United States)

    Barbot, Mariam; Meinecke, Michael

    2016-10-01

    Biological membranes exhibit function-related shapes, leading to a plethora of complex and beautiful cell and cell organellar morphologies. Most if not all of these structures have evolved for a particular physiological reason. The shapes of these structures are formed by physical forces that operate on membranes. To create particular shaped cells and cell organelles, membranes must undergo deformations which are determined by the structure and elasticity of the membrane and this process is most probable driven by proteins, lipids and/or interplay of both Zimmerberg and Kozlov (2006). Therefore, an important question of current cell biology in conjunction with physics and mathematics is to elucidate the functional cause for these different membrane morphologies as well as how they are formed. One of the most peculiar membrane shapes is observed in mitochondria. These organelles are surrounded by two membranes and especially the convoluted inner membrane displays a complex ultra-structure. A molecular understanding of how this membrane is shaped is missing to a large extent. Unlike membrane remodeling in classical curvature-dependent processes like clathrin-mediated endocytosis, mitochondria are most likely shaped by integral membrane proteins. Following, we will review the current knowledge of inner mitochondrial membrane architecture and discuss recent findings and advances in understanding the factors that shape this membrane. We will address pending questions especially with regard to the experimentally challenging nature of investigating membrane bending by hydrophobic integral membrane proteins. PMID:27456366

  5. Splanchnic artery aneurysms

    Directory of Open Access Journals (Sweden)

    Davidović Lazar B.

    2006-01-01

    Full Text Available Introduction. Splanchnic artery aneurysms are uncommon but important vascular entity because nearly 25% of all cases present as surgical emergency. Objective. The purpose of our study was to present nine patients operated on at the Institute of cardiovascular diseases, as well as literature review of clinical presentation of the disease. Method. There were three splenic artery aneurysms, two celiac trunk aneurysms, and one aneurysm of the hepatic, superior mesenteric, inferior mesenteric and gastroduodenal artery. All patients were males, mean aged 67.5 years (60-73. In four patients, splanchnic artery aneurysm was discovered accidentally during routine ultrasonographic and angiographic examinations of the abdominal aorta. At that time, arteriovenous fistula was diagnosed in a patient No 1; it was formed after rupture of the splenic artery aneurysm into the splenic vein. Three aneurysms were manifested by abdominal pain and palpable pulsating abdominal mass. Two patients were admitted as urgent cases in the state of hemorrhagic shock and signs of intraabdominal bleeding due to rupture of the splenic and hepatic arteries. In 7 cases, diagnosis was made preoperatively by means of ultrasonography and angiography; in two patients, accurate diagnosis was confirmed during surgery. Results. Proximal and distal ligation of the artery was performed in a patient with rupture of the splenic aneurysm into the splenic vein that caused arteriovenous fistula. Gastroduodenal artery aneurysm was treated by trans-aneurysmatic ligation of its "entering" and "exiting" branches. Aneurysms of distal part of the superior mesenteric and splenic artery were resected without further reconstruction. Partial resection of the aneurysm and endoaneurysmorrhaphy was carried out in one case of celiac trunk aneurysm, and in another, after aneurysm resection, the restoration of blood flow through the hepatic and lienal artery was achieved by Dacron grafts. In a patient with the

  6. Artery by Neuropeptides

    Directory of Open Access Journals (Sweden)

    Esmeralda Sofia Costa Delgado

    2012-01-01

    Methods. Isolated rabbit eyes (n=12 were perfused in situ with tyrode through the external ophthalmic artery. Effects of intra-arterial injections of NPY 200 μg/ml (Group A; n=6 and VIP 200 μg/ml (Group B; n=6 on the recorded pressure were obtained. For statistical analysis, Student's paired t-test and Fast Fourier Transform were used. Results. Spontaneous oscillations were observed before any drug administration in the 12 rabbit models. NPY produced an increase in total vascular resistance and a higher frequency and amplitude of oscillations, while VIP evoked the opposite effects. Conclusions. This study provides evidence of vasomotion in basal conditions in rabbit external ophthalmic artery. Concerning drug effects, NPY increased arterial resistance and enhanced vasomotion while VIP produced opposite effects which demonstrates their profound influence in arterial vasomotion.

  7. [Transposition of Great Artery].

    Science.gov (United States)

    Konuma, Takeshi; Shimpo, Hideto

    2015-07-01

    Transposition of the great artery is one of common congenital cardiac disease resulting cyanosis. Death occurs easily in untreated patients with transposition and intact ventricular septal defect (VSD) in infancy at a few days of age when posterior descending coronary artery (PDA) closed. Since there are 2 parallel circulations, flow from pulmonary to systemic circulation is necessary for systemic oxygenation, and Balloon atrial septostomy or prostaglandin infusion should be performed especially if patient do not have VSD. Although the advent of fetal echocardiography, it is difficult to diagnose the transposition of the great arteries (TGA) as abnormality of great vessels is relatively undistinguishable. The diagnosis of transposition is in itself an indication for surgery, and arterial switch procedure is performed in the case the left ventricle pressure remains more than 2/3 of systemic pressure. Preoperative diagnosis is important as associated anomalies and coronary artery branching patterns are important to decide the operative indication and timing of surgery.

  8. The relationship between eosinophilia and airway remodelling in mild asthma

    OpenAIRE

    Wilson, S J; Rigden, H.M.; Ward, J. A.; Laviolette, M.; Jarjour, N N; Djukanović, R.

    2013-01-01

    Background Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. Objective The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. Methods Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0–0....

  9. Collagen scaffold remodeling by human mesenchymal stem cells

    OpenAIRE

    Han, SJ; Chan, BP

    2011-01-01

    Type I collagen has been widely used as scaffold for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. We previously have developed a collagen microencapsulation technology entrapping many cells including human mesenchymal stem cells (hMSCs) in microspheres made of nanofibrous collagen meshwork. Nevertheless, little is understood about how stem cells interact with and remodel the collagen meshwork. This study aims to investigate collagen remodeling by...

  10. YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease

    DEFF Research Database (Denmark)

    Wang, Y.Z.; Ripa, R.S.; Johansen, J.S.;

    2008-01-01

    Background. YKL-40 is involved in remodelling and angiogenesis in non-cardiac inflammatory diseases. Aim was to quantitate plasma YKL-40 in patients with ST-elevation myocardial infarction (STEMI) or stable chronic coronary artery disease (CAD), and YKL-40 gene activation in human myocardium....... Methods and results. We included 73 patients: I) 20 patients with STEMI; II) 28 patients with stable CAD; III) 15 CAD patients referred for coronary by-pass surgery. YKL-40 mRNA expression was measured in myocardium subtended by stenotic or occluded arteries and areas with no apparent disease; and IV) 10...

  11. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice

    Directory of Open Access Journals (Sweden)

    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for α-smooth muscle actin (pixel/vessel. The ratio of right ventricle to left ventricle plus septum (RV/[LV+S] was used to determine right ventricular hypertrophy. Results Proliferative activity increased by 34% at day 4 in mice held under H (median: 0.38 compared to N (median: 0.28, p = 0.028 which was completely blocked by RAPA (median HO+RAPA: 0.23, p = 0.003. H-induced proliferation had leveled off within 3 weeks. At this time point media area had, however, increased by 53% from 91 (N to 139 (H, p Conclusion Therapy with rapamycin may represent a new strategy for the treatment of pulmonary hypertension.

  12. Effect of Intensive Blood Pressure Control on Cardiovascular Remodeling in Hypertensive Patients with Nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Otelio Randall

    2013-01-01

    Full Text Available Pulse pressure (PP, a marker of arterial system properties, has been linked to cardiovascular (CV complications. We examined (a association between unit changes of PP and (i composite CV outcomes and (ii development of left-ventricular hypertrophy (LVH and (b effect of mean arterial pressure (MAP control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102–107 mmHg or a lower MAP goal (≤92 mmHg and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11–1.47, P<0.01 and new LVH (RR = 1.26, CI = 1.04–1.54, P=0.02. PP increased at a greater rate in the usual than in lower MAP groups (slope ± SE: 1.08 ± 0.15 versus 0.42 ± 0.15 mmHg/year, P=0.002, but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health.

  13. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves

    OpenAIRE

    Lammers, Steven R.; Kao, Phil H.; Qi, H. Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R.; Shandas, Robin

    2008-01-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive ...

  14. Characterization of proximal pulmonary arterial cells from chronic thromboembolic pulmonary hypertension patients

    Directory of Open Access Journals (Sweden)

    Quarck Rozenn

    2012-03-01

    Full Text Available Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH is associated with proximal pulmonary artery obstruction and vascular remodeling. We hypothesized that pulmonary arterial smooth muscle (PASMC and endothelial cells (PAEC may actively contribute to remodeling of the proximal pulmonary vascular wall in CTEPH. Our present objective was to characterize PASMC and PAEC from large arteries of CTEPH patients and investigate their potential involvement in vascular remodeling. Methods Primary cultures of proximal PAEC and PASMC from patients with CTEPH, with non-thromboembolic pulmonary hypertension (PH and lung donors have been established. PAEC and PASMC have been characterized by immunofluorescence using specific markers. Expression of smooth muscle specific markers within the pulmonary vascular wall has been studied by immunofluorescence and Western blotting. Mitogenic activity and migratory capacity of PASMC and PAEC have been investigated in vitro. Results PAEC express CD31 on their surface, von Willebrand factor in Weibel-Palade bodies and take up acetylated LDL. PASMC express various differentiation markers including α-smooth muscle actin (α-SMA, desmin and smooth muscle myosin heavy chain (SMMHC. In vascular tissue from CTEPH and non-thromboembolic PH patients, expression of α-SMA and desmin is down-regulated compared to lung donors; desmin expression is also down-regulated in vascular tissue from CTEPH compared to non-thromboembolic PH patients. A low proportion of α-SMA positive cells express desmin and SMMHC in the neointima of proximal pulmonary arteries from CTEPH patients. Serum-induced mitogenic activity of PAEC and PASMC, as well as migratory capacity of PASMC, were increased in CTEPH only. Conclusions Modified proliferative and/or migratory responses of PASMC and PAEC in vitro, associated to a proliferative phenotype of PASMC suggest that PASMC and PAEC could contribute to proximal vascular remodeling in CTEPH.

  15. In vivo and in vitro measurements of pulmonary arterial stiffness: A brief review

    OpenAIRE

    Tian, Lian; Chesler, Naomi C.

    2012-01-01

    During the progression of pulmonary hypertension (PH), proximal pulmonary arteries (PAs) undergo remodeling such that they become thicker and the elastic modulus increases. Both of these changes increase the vascular stiffness. The increase in pulmonary vascular stiffness contributes to increased right ventricular (RV) afterload, which causes RV hypertrophy and eventually failure. Studies have found that proximal PA stiffness or its inverse, compliance, is strongly related to morbidity and mo...

  16. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Directory of Open Access Journals (Sweden)

    Chi-Li Chiu

    2013-01-01

    Full Text Available Extracellular matrix (ECM remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7, which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3. We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments.

  17. Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics.

    OpenAIRE

    Gray, R S; Cowan, P.; Di Mario, U.; Elton, R A; Clarke, B F; Duncan, L J

    1985-01-01

    Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in t...

  18. Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study.

    Science.gov (United States)

    Wu, Ji; Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian

    2015-10-01

    The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery-jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH. PMID:25595189

  19. Effects of Puerarin on Pulmonary Vascular Remodeling and Protein Kinase C-α in Chronic Cigarette Smoke Exposure Smoke-exposed Rats

    Institute of Scientific and Technical Information of China (English)

    Zhaoxia ZHU; Yongjian XU; Hui ZOU; Zhenxiang ZHANG; Wang NI; Shixin CHEN

    2008-01-01

    In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-α (PKC-α) in chronic exposure smoke rats, 54 male Wistar rats were randomly di- vided into 7 groups: control group (C group), smoke exposure groups (S4w group, Saw group), puer- arin groups (P4w group, P8w group), propylene glycol control groups (PC4w group,PC8w group). Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puer- arin. To evaluate vascular remodeling, alpha-smooth muscle actin (α-SM-actin) staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries (CMA/IAPA) which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcrip- tion-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were done to detect the PKC-α mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and α-SM-actin expres- sion were increased greatly, PASMC apoptosis was increased and proliferation was markedly in- creased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-ct mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the per- eentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-α mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an

  20. Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

    NARCIS (Netherlands)

    S.G. Swinnen; M.P. Dain; D. Mauricio; J.H. Devries; J.B. Hoekstra; F. Holleman

    2010-01-01

    We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 di