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Sample records for human aortic wall

  1. Aortic Wall Injury Related to Endovascular Therapy for Aortic Coarctation.

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    Tretter, Justin T; Jones, Thomas K; McElhinney, Doff B

    2015-09-01

    Aortic wall complications can occur in unrepaired aortic coarctation (CoA) and after surgical repair or endovascular treatment. This review summarizes the available literature and current understanding of aortic wall injury (AWI) surrounding the management of CoA, focusing specifically on acute and follow-up AWI after endovascular treatment. There have been 23 reported cases of aortic rupture after endovascular treatment for CoA, including angioplasty alone, bare metal stenting, and primary covered stent therapy. Even if these published cases represent only a minority of ruptures that have actually occurred, the incidence is substantially <1%. The incidence of acute aneurysm formation was 0% to 13% after angioplasty, 0% to 5% after bare metal stent placement, and <1% after covered stent placement. The reported incidence and natural history of both acute and new AWI during follow-up after endovascular therapy for CoA varies considerably, likely secondary to ascertainment and reporting biases and inconsistent definitions. Although important AWI after endovascular treatment of CoA seems to be declining in frequency with increasing experience and improving technology, it remains one of the most important potential adverse outcomes. Long-term surveillance for new AWI and monitoring of existing AWI is mandatory, with institution of appropriate treatment when necessary. A central research focus in this population should be determination of the appropriate treatment for both native and recurrent CoA across various ages with regard to limiting recurrent CoA and preventing associated aortic wall complications, in addition to determining the appropriate treatment of various AWI. Consistent definitions and reporting are necessary to truly understand the incidence of, risk factors for, and measures protective against AWI after angioplasty or stent implantation for CoA.

  2. Decreased expression of fibulin-4 in aortic wall of aortic dissection.

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    Huawei, P; Qian, C; Chuan, T; Lei, L; Laing, W; Wenlong, X; Wenzhi, L

    2014-02-01

    In this research, we will examine the expression of Fibulin-4 in aortic wall to find out its role in aortic dissection development. The samples of aortic wall were obtained from 10 patients operated for acute ascending aortic dissection and five patients for chronic ascending aortic dissection. Another 15 pieces of samples from patients who had coronary artery bypass were as controls. The aortic samples were stained with aldehyde magenta dyeing to evaluate the arrangement of elastic fibers. The Fibulin-4 protein and mRNA expression were both determined by Western blot and realtime quantitative polymerase chain reaction. Compared with the control group, both in acute and chronic ascending aortic dissection, elastic fiber fragments increased and the expression of fibulin-4 protein significantly decreased (P= 0.045 < 0.05). The level of fibulin-4 mRNA decreased in acute ascending aortic dissection (P= 0.034 < 0.05), while it increased in chronic ascending aortic dissection (P=0.004 < 0.05). The increased amounts of elastic fiber fragments were negatively correlated with the expression of fibulin-4 mRNA in acute ascending aortic dissection. In conclusion, in aortic wall of ascending aortic dissection, the expression of fibulin-4 protein decreased and the expression of fibulin-4 mRNA was abnormal. Fibulin-4 may play an important role in the pathogenesis of aortic dissection.

  3. Ascending aortic wall cohesion: comparison of bicuspid and tricuspid valves.

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    Benedik, Jaroslav; Pilarczyk, Kevin; Wendt, Daniel; Indruch, Jiri; Flek, Radek; Tsagakis, Konstantinos; Alaeddine, Savvas; Jakob, Heinz

    2012-01-01

    Objectives. Bicuspid aortic valve (AV) represents the most common form of congenital AV malformation, which is frequently associated with pathologies of the ascending aorta. We compared the mechanical properties of the aortic wall between patients with bicuspid and tricuspid AV using a new custom-made device mimicking transversal aortic wall shear stress. Methods. Between 03/2010 and 07/2011, 190 consecutive patients undergoing open aortic valve replacement at our institution were prospectively enrolled, presenting either with a bicuspid (group 1, n = 44) or a tricuspid (group 2, n = 146) AV. Aortic wall specimen were examined with the "dissectometer" resulting in nine specific aortic-wall parameters derived from tensile strength curves (TSC). Results. Patients with a bicuspid AV showed significantly more calcified valves (43.2% versus 15.8%, P group (P = 0.003, P = 0.02, P = 0.01). We found no difference in the aortic wall cohesion between both groups as revealed by shear stress testing (P = 0.72, P = 0.40, P = 0.41). Conclusion. We observed no differences of TSC in patients presenting with tricuspid or bicuspid AVs. These results may allow us to assume that the morphology of the AV and the pathology of the ascending aorta are independent.

  4. Finite Element Implementation of a Structurally-Motivated Constitutive Relation for the Human Abdominal Aortic Wall with and without Aneurysms

    DEFF Research Database (Denmark)

    Enevoldsen, Marie Sand; Henneberg, Kaj-Åge; Lönn, L

    2011-01-01

    The structural integrity of the abdominal aorta is maintained by elastin, collagen, and vascular smooth muscle cells. Changes with age in the structure can lead to develop-ment of aneurysms. This paper presents initial work to capture these changes in a finite element model (FEM) of a structural......-ly-motivated anisotropic constitutive relation for the “four fiber family” arterial model. First a 2D implementation is used for benchmarking the FEM implementation to fitted biaxial stress-strain data obtained experimentally from four different groups of persons; 19-29 years, 30-60 years, 61-79 years and abdominal aortic...

  5. Improving the efficiency of abdominal aortic aneurysm wall stress computations.

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    Zelaya, Jaime E; Goenezen, Sevan; Dargon, Phong T; Azarbal, Amir-Farzin; Rugonyi, Sandra

    2014-01-01

    An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses.

  6. Association between osteopontin and human abdominal aortic aneurysm.

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    Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

    2007-03-01

    In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

  7. Proteomic identification of differentially expressed proteins in aortic wall of patients with ruptured and nonruptured abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Lindholt, Jes S.; Vorum, Henrik

    2009-01-01

    To compare the basic proteomic composition of abdominal aortic aneurysm (AAA) wall tissue in patients with nonruptured and ruptured aneurysms.......To compare the basic proteomic composition of abdominal aortic aneurysm (AAA) wall tissue in patients with nonruptured and ruptured aneurysms....

  8. Wall shear stress indicators in abnormal aortic geometries

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    Prahl Wittberg, Lisa; van Wyk, Stevin; Fuchs, Laszlo; Gutmark, Ephraim; Gutmark-Little, Iris

    2015-11-01

    Cardiovascular disease, such as atherosclerosis, occurs at specific locations in the arterial tree. Characterizing flow and forces at these locations is crucial to understanding the genesis of disease. Measures such as time average wall shear stress, oscillatory shear index, relative residence time and temporal wall shear stress gradients have been shown to identify plaque prone regions. The present paper examines these indices in three aortic geometries obtained from patients whose aortas are deformed due to a genetic pathology and compared to one normal geometry. This patient group is known to be prone to aortic dissection and our study aims to identify early indicators that will enable timely intervention. Data obtained from cardiac magnetic resonance imaging is used to reconstruct the aortic arch. The local unsteady flow characteristics are calculated, fully resolving the flow field throughout the entire cardiac cycle. The Quemada model is applied to account for the non-Newtonian properties of blood, an empirical model valid for different red blood cell loading. The impact of the deformed aortic geometries is analyzed to identify flow patterns that could lead to arterial disease at certain locations.

  9. Effects of the flexibility of the arterial wall on the wall shear stresses and wall tension in Abdominal Aortic Aneurysms.

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    Salsac, Anne-Virginie; Fernandez, Miguel; Chomaz, Jean-Marc

    2005-11-01

    As an abdominal aortic aneurysm develops, large changes occur in the composition and structure of the arterial wall, which result in its stiffening. So far, most studies, whether experimental or numerical, have been conducted assuming the walls to be rigid. A numerical simulation of the fluid structure interactions is performed in different models of aneurysms in order to analyze the effects that the wall compliance might have on the flow topology. Both symmetric and non-symmetric models of aneurysms are considered, all idealistic in shape. The wall mechanical properties are varied in order to simulate the progressive stiffening of the walls. The spatial and temporal distributions of wall tension are calculated for the different values of the wall elasticity and compared to the results for the rigid walls. In the case of rigid walls, the calculation of the wall shear stresses and pressure compare very well with experimental results.

  10. Using The Descending Aortic Wall Thickness Measured In Transesophageal Echocardiography As A Risk Marker For Aortic Dissection

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    Zaher Fanari

    2015-04-01

    Full Text Available Objective: The aim of this study is to estimate whether aortic wall thickness is increased in patients with Aortic dissection (AD compared to low risk control group and can be used in addition to aortic diameter as a risk marker of AD. Background: AD occurs due to pathologies that may increase thickness of the aortic wall. Transesophageal echocardiography (TEE has the ability to visualise both the thoracic aortic wall and lumen. Aortic diameter has been used to predict aortic dissection and timing of surgery, but it is not always predictive of that risk. Methods: In 48 patients with AD who underwent TEE were examined retrospectively and compared to 48 control patients with patent foramen ovale (PFO. We measured aortic diameter at different levels, intimal/medial thickness (IMT and complete wall thickness (CMT. Demographic data and cardiovascular risk factors were reviewed. The data was analysed using ANOVA and student t test. Results: (AD patients were older [mean age 66 AD vs. 51 PFO], had more hypertension, diabetes, hyperlipidemia and Coronary artery disease. Both IMT and CMT in the descending aorta were increased in AD group [(1.85 vs. 1.43 mm; P=0.03 and 2.93 vs. 2.46 mm; p=0.01. As expected the diameter of ascending aorta was also greater in AD (4.61 vs. 2.92 cm; P=0.004. Conclusions: CMT and IMT in the descending aorta detected by TEE is greater in patients with AD when compared to control and may add prognostic data to that of aortic diameter

  11. Partially uncovered Cheatham platinum-covered stent to treat complex aortic coarctation associated with aortic wall aneurysm.

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    Butera, Gianfranco; Piazza, Luciane

    2015-04-01

    Percutaneous treatment of aortic coarctation is a widely used option. Covered stents have increased the profile of efficacy and safety of this procedure. Here we report on a 32-year-old woman with significant aortic recoarctation associated with aortic wall aneurysm and close proximity of both lesions to the origin of both the subclavian arteries. It was decided to manually and partially uncover the proximal part of the stent to have a hybrid stent that could act as a bare stent at the level of the origin of the subclavian arteries and as a covered stent at the level of the aneurysm.

  12. Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity

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    Samantha K Atkins; Alison N Moore; Philippe Sucosky

    2016-01-01

    AIM: To investigate the role of type-I left-right bicuspid aortic valve(LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta(AA) concavity, in the absence of underlying genetic or structural defects.METHODS: Transient wall shear stress(WSS) profiles in the concavity of tricuspid aortic valve(TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal(nondilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase(MMP) expression and activity via immunostaining and gelatin zymography.RESULTS: Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS(P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity(total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS(P = 0.08, P = 0.15 and P = 0.59, respectively).CONCLUSION: The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA.

  13. Assessment of aortic wall stiffness in patients with Familial Mediterranean Fever.

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    Tavil, Yusuf; Oztürk, Mehmet Akif; Ureten, Kemal; Sen, Nihat; Kaya, Mehmet Güngör; Cemri, Mustafa; Cengel, Atiye

    2008-05-01

    To evaluate aortic wall stiffness and its relation between the aortic stiffness and the left ventricular function in patients with Familial Mediterranean Fever (FMF). The study population was composed of 31 patients with FMF in attack-free period (12 men, 19 women; mean age: 36+/-7 years) and 27 healthy subjects (10 men, 17 women; mean age: 34+/-7 years) who had volunteered to participate. Aortic stiffness indices, aortic strain and distensibility, were calculated from the aortic diameters measured by echocardiography and blood pressure obtained by sphygmomanometry. There were significant differences between the control and the patient group in aortic strain (mean (SD), 7.23+/-2.14 versus 4.91+/-1.66%, p=0.01) and distensibility (4.02+/-1.42 versus 2.84+/-1.46, 10(-6)cm(2)dyn(-1), p=0.001). Although there was no correlation between the aortic stiffness parameters and the left ventricular function parameters, there were significant negative correlations between the disease duration and aortic strain index (r=-0.29, p<0.001), and between the disease duration and distensibility (r=-0.32, p<0.001). Aortic stiffness measurements were found abnormal in patients with FMF. We have also demonstrated that there were significant correlations between aortic stiffness parameters and disease duration.

  14. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans.

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    Lee, Vivian S; Halabi, Carmen M; Hoffman, Erin P; Carmichael, Nikkola; Leshchiner, Ignaty; Lian, Christine G; Bierhals, Andrew J; Vuzman, Dana; Mecham, Robert P; Frank, Natasha Y; Stitziel, Nathan O

    2016-08-01

    Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.

  15. Aortic aneurysm after patch aortoplasty for coarctation: analysis of patch size and wall growth.

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    Al-Hroob, A; Husayni, T S; Freter, A; Chiemmongkoltip, P; Ilbawi, M N; Arcilla, R A

    2003-01-01

    Aortic aneurysm may develop after surgery for coarctation of aorta especially patch aortoplasty. The size of patch and of adjacent native aortic wall was analyzed to determine whether aortic dilatation represents a true aneurysm. Electron beam tomography (EBT) was done on 19 patients, three months to 17.5 years after patch aortoplasty. Tomograms of aorta were obtained in 6-mm slices, and maximal cross-sectional area was digitized to obtain: total circumference (Ct), patch component (Cp), and aortic wall component (Cw). Ct, Cp, and Cw were normalized to the circumference of distal aorta (Cda) as: isthmus/distal aorta (Ct/Cda), patch segment/distal aorta (Cp/Cda), wall segment/distal aorta (Cw/Cda). Ct/Cda ranged from 109% to 260%. In 12 patients (group A), it varied from 168% to 260%; and in seven (group B), 109% to 133%. There was strong correlation (r = 0.92) between Ct/Cda and Cp/Cda. Ct/Cda, Cp/Cda, and Cp/Cw were higher in group A than B (p <0.001) but Cw/Cda did not differ. Cw/Cda was greater than the coarctation/distal aorta diameter ratios of preoperative angiograms, consistent with accelerated aortic wall growth postsurgery. No definite aneurysm was seen. Localized dilatation of aorta following patch aortoplasty in children is primarily due to a large synthetic patch and, partly, to increased aortic wall growth. Serial EBT or magnetic resonance imaging is indicated to monitor aortic wall growth and occurrence of aneurysm.

  16. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein.

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    Navab, M; Imes, S S; Hama, S Y; Hough, G P; Ross, L.A.; Bork, R W; Valente, A. J.; Berliner, J A; Drinkwater, D C; Laks, H

    1991-01-01

    Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from t...

  17. Simulations of blood flow in patient-specific aortic dissections with a deformable wall model

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    Baeumler, Kathrin; Vedula, Vijay; Sailer Karmann, Anna; Marsden, Alison; Fleischmann, Dominik

    2016-11-01

    Aortic dissection is a life-threatening condition in which blood penetrates into the vessel wall, creating a second flow channel, often requiring emergency surgical repair. Up to 50% of patients who survive the acute event face late complications like aortic dilatation and eventual rupture. Prediction of late complications, however, remains challenging. We therefore aim to perform accurate and reliable patient-specific simulations of blood flow in aortic dissections, validated by 4D-Flow MRI. Among other factors, this is a computational challenge due to the compliance of the vessel walls and the large degree of membrane deformation between the two flow channels. We construct an anatomic patient-specific model from CT data including both flow channels and the membrane between them. We then run fluid structure interaction simulations using an arbitrary Lagrangian-Eulerian (ALE) formulation within a multiscale variational framework, employing stabilized finite element methods. We compare hemodynamics between a rigid and a deformable wall model and examine membrane dynamics and pressure differences between the two flow channels. The study focuses on the computational and modeling challenges emphasizing the importance of employing a deformable wall model for aortic dissections.

  18. Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats.

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    Ruseva, Boryana; Atanasova, Milena; Tsvetkova, Reni; Betova, Tatyana; Mollova, Margarita; Alexandrova, Margarita; Laleva, Pavlina; Dimitrova, Aneliya

    2015-01-01

    Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR.

  19. Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

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    Boryana Ruseva

    2015-01-01

    Full Text Available Selenium (Se is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR. Sixteen male Wistar Kyoto (WKY rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1 activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR.

  20. Morphological evidence for a change in the pattern of aortic wall shear stress with age.

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    Bond, Andrew R; Iftikhar, Saadia; Bharath, Anil A; Weinberg, Peter D

    2011-03-01

    The distribution of atherosclerosis around branch sites changes with age in human and rabbit aortas. We tested whether that reflects a change in the pattern of wall shear stress by examining shear-dependent morphological features of endothelial cells. Endothelial cells and their nuclei align and elongate with applied shear. These parameters were examined in the descending thoracic aorta of immature and mature rabbits. The use of Häutchen preparations, fluorescent stains, and automated image analysis allowed nuclear morphology to be mapped reliably at high resolution over large areas. Cells and their nuclei were most elongated downstream of branch ostia in immature aortas but upstream of them in mature aortas. Elongation was generally greater in mature animals, and nuclei aligned toward the ostia more in these animals, consistent with a greater flow into the branch. Morphology away from branches was indicative of helical flow in the aorta, with greatest shear on the dorsal wall, at both ages. The data are consistent with age-related changes in the pattern of shear around aortic branches. Maps of nuclear elongation closely resembled maps of lesion frequency. The association was positive, implying that lesions occur at sites of high shear stress at both ages.

  1. Quantification of progression and regression of descending thoracic aortic wall thickness by enhanced computed tomography

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    Yokoyama, Kenichi; Takasu, Junichiro; Yamamoto, Rie; Taguchi, Rie; Itani, Yasutaka; Ito, Yuichi; Watanabe, Shigeru; Masuda, Yoshiaki [Chiba Univ. (Japan). School of Medicine

    2001-04-01

    The purpose of this study is to verify the usefulness of the quantification of aortic wall involvement by enhanced computed tomography (CT). One-hundred thirteen Japanese patients underwent two enhanced CT of the descending thoracic aorta at intervals. We sliced the descending thoracic aorta continuously from the level of the tracheal bifurcation with 1 cm intervals, and we defined aortic wall volume (AWV) (cm{sup 3}) as the sum of a 7-slice area of aortic wall involving calcification. The average of AWV increased from 7.95{+-}2.92 cm{sup 3} to 8.70{+-}2.98 cm{sup 3}. The developmental rate of AWV ({delta}AWV) was 0.270{+-}0.281 cm{sup 3}/year. {delta}AWV did not have a significant correlation with any risk factor at the baseline. {delta}AWV had significant correlation with total cholesterol, (LDL-C) low-density lipoprotein cholesterol and LDL-C/(HDL-C) high-density lipoprotein cholesterol ratio at the follow-up, and by multivariate analysis with only the LDL-C/HDL-C ratio. {delta}AWV was not correlated with the intake status of hypoglycemic, antihypertensive or lipid-lowering drugs. The cut-off level of total cholesterol with the most significant odds ratio for progression of aortic wall was 190 mg/dl, and that of LDL-C was 130 mg/dl. This method proved to be useful for the non-invasive assessment of aortic wall thickness. (author)

  2. Correlation of echocardiographic wall stress and left ventricular pressure and function in aortic stenosis.

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    DePace, N L; Ren, J F; Iskandrian, A S; Kotler, M N; Hakki, A H; Segal, B L

    1983-04-01

    Previous studies have suggested that left ventricular pressure (P) can be predicted in patients with aortic stenosis by the equation P = 235 h/r, where 235 is a constant peak wall stress (sigma), h is end-systolic wall thickness, and r is end-systolic dimension/2; h and r are measured by M-mode echocardiography. In 73 patients with aortic stenosis (valve area less than 0.7 cm2), measured and predicted left ventricular pressure correlated poorly (r = 0.17). The measured wall stress in our patients varied from 120 to 250 mm Hg in patients with normal left ventricular function and from 250 to 550 mm Hg in patients with abnormal function. The correlation between sigma and h was only fair (r = 0.53), because many patients had inappropriate left ventricular hypertrophy. There was a statistically significant correlation between ejection fraction and sigma (r = 0.62) and between ejection fraction and end-systolic dimension (r = -0.70), but there was considerable scatter of ejection fractions for any given end-systolic dimension. We conclude that sigma is not constant in aortic stenosis, and the use of a constant sigma to predict left ventricular pressure is unreliable; inappropriate left ventricular hypertrophy may explain why sigma is not constant. M-mode echocardiography is not reliable in assessing the severity of aortic stenosis in adults; such assessment requires precise measurements of pressure gradients and flow by cardiac catheterization.

  3. Method for aortic wall strain measurement with three-dimensional ultrasound speckle tracking and fitted finite element analysis.

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    Karatolios, Konstantinos; Wittek, Andreas; Nwe, Thet Htar; Bihari, Peter; Shelke, Amit; Josef, Dennis; Schmitz-Rixen, Thomas; Geks, Josef; Maisch, Bernhard; Blase, Christopher; Moosdorf, Rainer; Vogt, Sebastian

    2013-11-01

    Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain. Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system. Longitudinal and circumferential strains were computed offline with high spatial resolution using a customized commercial speckle-tracking software and finite element analysis. Indices for spatial heterogeneity and systolic dyssynchrony were determined for healthy abdominal aortas and abdominal aneurysms. All examined aortic wall segments exhibited considerable heterogenous in-plane strain distributions. Higher spatial resolution of strain imaging resulted in the detection of significantly higher local peak strains (p ≤ 0.01). In comparison with healthy abdominal aortas, aneurysms showed reduced mean strains and increased spatial heterogeneity and more pronounced temporal dyssynchrony as well as delayed systole. Three-dimensional ultrasound speckle tracking enables the analysis of spatially highly resolved strain fields of the aortic wall and offers the potential to detect local aortic wall motion deformations and abnormalities. These data allow the definition of new indices by which the different biomechanical properties of healthy aortas and aortic aneurysms can be characterized. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Christopher Gestrich

    2015-01-01

    Full Text Available Human aortic aneurysms have been associated with inflammation and vascular remodeling. Since the endocannabinoid system modulates inflammation and tissue remodeling, we investigated its components in human aortic aneurysms. We obtained anterior aortic wall samples from patients undergoing elective surgery for aortic aneurysm or coronary artery disease as controls. Histological and molecular analysis (RT-qPCR was performed, and endocannabinoid concentration was determined using LC-MRM. Patient characteristics were comparable between the groups except for a higher incidence of arterial hypertension and diabetes in the control group. mRNA level of cannabinoid receptors was significantly higher in aneurysms than in controls. Concentration of the endocannabinoid 2-arachidonoylglycerol was significantly higher, while the second endocannabinoid anandamide and its metabolite arachidonic acid and palmitoylethanolamide were significantly lower in aneurysms. Histology revealed persistent infiltration of newly recruited leukocytes and significantly higher mononuclear cell density in adventitia of the aneurysms. Proinflammatory environment in aneurysms was shown by significant upregulation of M-CSF and PPARγ but associated with downregulation of chemokines. We found comparable collagen-stained area between the groups, significantly decreased mRNA level of CTGF, osteopontin-1, and MMP-2, and increased TIMP-4 expression in aneurysms. Our data provides evidence for endocannabinoid system activation in human aortic aneurysms, associated with persistent low-level inflammation and vascular remodeling.

  5. Pressure dependency of aortic pulse wave velocity in vivo is not affected by vasoactive substances that alter aortic wall tension ex vivo.

    Science.gov (United States)

    Butlin, Mark; Lindesay, George; Viegas, Kayla D; Avolio, Alberto P

    2015-05-15

    Aortic stiffness, a predictive parameter in cardiovascular medicine, is blood pressure dependent and experimentally requires isobaric measurement for meaningful comparison. Vasoactive drug administration to change peripheral resistance and blood pressure allows such isobaric comparison but may alter large conduit artery wall tension, directly changing aortic stiffness. This study quantifies effects of sodium nitroprusside (SNP, vasodilator) and phenylephrine (PE, vasoconstrictor) on aortic stiffness measured by aortic pulse wave velocity (aPWV) assessed by invasive pressure catheterization in anaesthetized Sprague-Dawley rats (n = 7). This was compared with nondrug-dependent alteration of blood pressure through reduced venous return induced by partial vena cava occlusion. In vivo drug concentration was estimated by modeling clearance rates. Ex vivo responses of excised thoracic and abdominal aortic rings to drugs was measured using myography. SNP administration did not alter aPWV compared with venous occlusion (P = 0.21-0.87). There was a 5% difference in aPWV with PE administration compared with venous occlusion (P arteries in vivo. However, similar drug concentrations affect aortic ring wall tension ex vivo. Future studies investigating in vivo and ex vivo kinetics will need to elucidate mechanisms for this marked difference.

  6. MRI-based Determination of Reference Values of Thoracic Aortic Wall Thickness in a General Population

    Energy Technology Data Exchange (ETDEWEB)

    Mensel, Birger; Quadrat, Alexander; Schneider, Tobias; Kuehn, Jens-Peter; Hegenscheid, Katrin [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Doerr, Marcus [University Medicine Greifswald, Department of Internal Medicine, Greifswald (Germany); DZHK (German Center for Cardiovascular Research), Greifswald (Germany); Voelzke, Henry [University Medicine Greifswald, Institute for Community Medicine, Greifswald (Germany); DZHK (German Center for Cardiovascular Research), Greifswald (Germany); Lieb, Wolfgang [Christian Albrechts University, Institute of Epidemiology, Kiel (Germany); Lorbeer, Roberto [University Medicine Greifswald, Institute for Community Medicine, Greifswald (Germany)

    2014-09-15

    To provide age- and sex-specific reference values for MRI-derived wall thickness of the ascending and descending aorta in the general population. Data of 753 subjects (311 females) aged 21-81 years were analysed. MRI was used to determine the aortic wall thickness (AWT). Equations for reference value calculation according to age were established for females and males. Median wall thickness of the ascending aorta was 1.46 mm (5th-95th range: 1.15-1.88 mm) for females and 1.56 mm (1.22-1.99 mm) for males. Median wall thickness of the descending aorta was 1.26 mm (0.97-1.58 mm) in females and 1.36 mm (1.04-1.75 mm) in males. While median and 5th and 95th percentiles for the ascending and descending aorta increased with age in both sexes, the association between age and median AWT was stronger in males than in females for both the ascending and descending aorta. Reference values for the ascending and descending AWT are provided. In a healthy sample from the general population, the wall of the ascending aorta is thicker than the wall of the descending aorta, and both walls are thicker in males than females. The increase in wall thickness with age is greater in males. (orig.)

  7. Impact of poroelasticity of intraluminal thrombus on wall stress of abdominal aortic aneurysms

    Directory of Open Access Journals (Sweden)

    Polzer Stanislav

    2012-08-01

    Full Text Available Abstract Background The predictions of stress fields in Abdominal Aortic Aneurysm (AAA depend on constitutive descriptions of the aneurysm wall and the Intra-luminal Thrombus (ILT. ILT is a porous diluted structure (biphasic solid–fluid material and its impact on AAA biomechanics is controversially discussed in the literature. Specifically, pressure measurements showed that the ILT cannot protect the wall from the arterial pressure, while other (numerical and experimental studies showed that at the same time it reduces the stress in the wall. Method To explore this phenomenon further a poroelastic description of the ILT was integrated in Finite Element (FE Models of the AAA. The AAA model was loaded by a pressure step and a cyclic pressure wave and their transition into wall tension was investigated. To this end ILT’s permeability was varied within a microstructurally motivated range. Results The two-phase model verified that the ILT transmits the entire mean arterial pressure to the wall while, at the same time, it significantly reduces the stress in the wall. The predicted mean stress in the AAA wall was insensitive to the permeability of the ILT and coincided with the results of AAA models using a single-phase ILT description. Conclusion At steady state, the biphasic ILT behaves like a single-phase material in an AAA model. Consequently, computational efficient FE single-phase models, as they have been exclusively used in the past, accurately predict the wall stress in AAA models.

  8. Multimodal optical measurement in vitro of surface deformations and wall thickness of the pressurized aortic arch.

    Science.gov (United States)

    Genovese, Katia; Humphrey, Jay D

    2015-04-01

    Computational modeling of arterial mechanics continues to progress, even to the point of allowing the study of complex regions such as the aortic arch. Nevertheless, most prior studies assign homogeneous and isotropic material properties and constant wall thickness even when implementing patient-specific luminal geometries obtained from medical imaging. These assumptions are not due to computational limitations, but rather to the lack of spatially dense sets of experimental data that describe regional variations in mechanical properties and wall thickness in such complex arterial regions. In this work, we addressed technical challenges associated with in vitro measurement of overall geometry, full-field surface deformations, and regional wall thickness of the porcine aortic arch in its native anatomical configuration. Specifically, we combined two digital image correlation-based approaches, standard and panoramic, to track surface geometry and finite deformations during pressurization, with a 360-deg fringe projection system to contour the outer and inner geometry. The latter provided, for the first time, information on heterogeneous distributions of wall thickness of the arch and associated branches in the unloaded state. Results showed that mechanical responses vary significantly with orientation and location (e.g., less extensible in the circumferential direction and with increasing distance from the heart) and that the arch exhibits a nearly linear increase in pressure-induced strain up to 40%, consistent with other findings on proximal porcine aortas. Thickness measurements revealed strong regional differences, thus emphasizing the need to include nonuniform thicknesses in theoretical and computational studies of complex arterial geometries.

  9. Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

    OpenAIRE

    2015-01-01

    Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequ...

  10. A comparison of modelling techniques for computing wall stress in abdominal aortic aneurysms

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    McGloughlin Timothy M

    2007-10-01

    Full Text Available Abstract Background Aneurysms, in particular abdominal aortic aneurysms (AAA, form a significant portion of cardiovascular related deaths. There is much debate as to the most suitable tool for rupture prediction and interventional surgery of AAAs, and currently maximum diameter is used clinically as the determining factor for surgical intervention. Stress analysis techniques, such as finite element analysis (FEA to compute the wall stress in patient-specific AAAs, have been regarded by some authors to be more clinically important than the use of a "one-size-fits-all" maximum diameter criterion, since some small AAAs have been shown to have higher wall stress than larger AAAs and have been known to rupture. Methods A patient-specific AAA was selected from our AAA database and 3D reconstruction was performed. The AAA was then modelled in this study using three different approaches, namely, AAA(SIMP, AAA(MOD and AAA(COMP, with each model examined using linear and non-linear material properties. All models were analysed using the finite element method for wall stress distributions. Results Wall stress results show marked differences in peak wall stress results between the three methods. Peak wall stress was shown to reduce when more realistic parameters were utilised. It was also noted that wall stress was shown to reduce by 59% when modelled using the most accurate non-linear complex approach, compared to the same model without intraluminal thrombus. Conclusion The results here show that using more realistic parameters affect resulting wall stress. The use of simplified computational modelling methods can lead to inaccurate stress distributions. Care should be taken when examining stress results found using simplified techniques, in particular, if the wall stress results are to have clinical importance.

  11. Fabrication of a compliant phantom of the human aortic arch for use in Particle Image Velocimetry (PIV experimentation

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    Hütter Larissa

    2016-09-01

    Full Text Available Compliant phantoms of the human aortic arch can mimic patient specific cardiovascular dysfunctions in vitro. Hence, phantoms may enable elucidation of haemodynamic disturbances caused by aortic dysfunction. This paper describes the fabrication of a thin-walled silicone phantom of the human ascending aorta and brachiocephalic artery. The model geometry was determined via a meta-analysis and modelled in SolidWorks before 3D printing. The solid model surface was smoothed and scanned with a 3D scanner. An offset outer mould was milled from Ebalta S-Model board. The final phantom indicated that ABS was a suitable material for the internal model, the Ebalta S-Model board yielded a rough external surface. Co-location of the moulds during silicone pour was insufficient to enable consistent wall thickness. The resulting phantom was free of air bubbles but did not have the desired wall thickness consistency.

  12. M型超声检测腹主动脉前后壁运动的初步研究%Primary studies of anteroposterior abdominal aortic wall motion with M-mode ultrasound

    Institute of Scientific and Technical Information of China (English)

    辛群; 蔡珠虹; 包俊敏; 梅志军; 景在平

    2011-01-01

    Objective To find out the characteristics of anteroposterior abdominal aortic wall motion and to consider the potential implications of such variations. Methods M-mode ultrasound was used to measure abdominal aortic wall motion in human (n=20) and 2 animal species [dogs (n=8), and pigs (n=5)]. Anterior wall displacement (da),posterior wall displacement (dp), and diastolic diameter (Da) were measured. The ratio of displacement to the diameter was calculated (da/Dd. and dp/Dd). Results Aortic diameter varied from to (6.34±0.84) mm (dog) to (13.76±1.11) mm (human).Anterior wall displacement was about 3 times greater than the posterior among the species studied. The ratio of wall displacement to diastolic diameter were similar for the anterior and posterior walls. Wall displacement increased linearly with the diameter. Conclusions Abdominal aortic wall dynamics are similar in humans and animals regardless of the aortic size, with more anterior than posterior wall motion. These data suggest increased .dynamic strain of the anterior wall,which may help explain why human abdominal aortic aneurysms initially develop anteriorly. Haemodynamies plays an important role in the abdominal aortic aneurysm pathogenesis.%目的:应用M型超声观测正常腹主动脉前后壁运动的特征.方法:采集健康人组、健康犬组、健康猪组腹主动脉的M型超声图像,测量动脉前壁和后壁振幅(da和dP)、舒张期动脉直径(Dd),取其平均值;并分别计算各组数值:前壁振幅/舒张期动脉直径(da/Dd),后壁振幅/舒张期动脉直径(dp/Dd).结果:三组结果显示腹主动脉前壁振幅高于后壁振幅,差异有统计学意义(P<0.01).各组中管壁振幅与管径呈正相关.da/Dd和dp/Dd组间比较,差异无统计学意义.结论:正常腹主动脉前、后壁的运动差异与腹主动脉瘤的形成有一定关系,提示血液动力学因素在腹主动脉瘤发病机制中起着重要作用.

  13. A simple, effective and clinically applicable method to compute abdominal aortic aneurysm wall stress.

    Science.gov (United States)

    Joldes, Grand Roman; Miller, Karol; Wittek, Adam; Doyle, Barry

    2016-05-01

    Abdominal aortic aneurysm (AAA) is a permanent and irreversible dilation of the lower region of the aorta. It is a symptomless condition that if left untreated can expand to the point of rupture. Mechanically-speaking, rupture of an artery occurs when the local wall stress exceeds the local wall strength. It is therefore desirable to be able to non-invasively estimate the AAA wall stress for a given patient, quickly and reliably. In this paper we present an entirely new approach to computing the wall tension (i.e. the stress resultant equal to the integral of the stresses tangent to the wall over the wall thickness) within an AAA that relies on trivial linear elastic finite element computations, which can be performed instantaneously in the clinical environment on the simplest computing hardware. As an input to our calculations we only use information readily available in the clinic: the shape of the aneurysm in-vivo, as seen on a computed tomography (CT) scan, and blood pressure. We demonstrate that tension fields computed with the proposed approach agree well with those obtained using very sophisticated, state-of-the-art non-linear inverse procedures. Using magnetic resonance (MR) images of the same patient, we can approximately measure the local wall thickness and calculate the local wall stress. What is truly exciting about this simple approach is that one does not need any information on material parameters; this supports the development and use of patient-specific modelling (PSM), where uncertainty in material data is recognised as a key limitation. The methods demonstrated in this paper are applicable to other areas of biomechanics where the loads and loaded geometry of the system are known. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. In vivo mechanical properties of thoracic aortic aneurysmal wall estimated from in vitro biaxial tensile test.

    Science.gov (United States)

    Fukui, Tomohiro; Matsumoto, Takeo; Tanaka, Toshihiro; Ohashi, Toshiro; Kumagai, Kiichiro; Akimoto, Hiroji; Tabayashi, Koichi; Sato, Masaaki

    2005-01-01

    To investigate the mechanism of aneurysm rupture, it is necessary to examine the mechanical properties of aneurysm tissues in vivo. A new approach to evaluate in vivo mechanical properties of aortic aneurysmal tissues has been proposed in this study. The shape of the aneurysm was modeled as a sphere, and equi-biaxial stress in the in vivo state was estimated from the diameter and the wall thickness of each aneurysm and mean blood pressure of each patient. The mechanical properties of the aneurysm at the in vivo stress were estimated from its in vitro biaxial tensile properties. There were no significant correlations among maximum diameter D, wall thickness t, and mean infinitesimal strain in the in vivo state epsilon(m). This indicates the wall deformation during aneurysm development was not elastic but plastic. The mean incremental elastic modulus H(m), an index of tissue stiffness, had a significant positive correlation with elastic modulus anisotropy index K(H). This indicates the aneurysmal wall got more anisotropic in vivo as it becomes stiffer.

  15. Quantitative Assessment of Wall Shear Stress in an Aortic Coarctation - Impact of Virtual Interventions

    Science.gov (United States)

    Karlsson, Matts; Andersson, Magnus; Lantz, Jonas

    2014-11-01

    Turbulent and wall impinging blood flow causes abnormal shear forces onto the lumen and may play an important role in the pathogenesis of numerous cardiovascular diseases. In the present study, wall shear stress (WSS) and related flow parameters were studied in a pre-treated aortic coarctation (CoA) as well as after several virtual interventions using computational fluid dynamics (CFD). Patient-specific geometry and flow conditions were derived from magnetic resonance imaging (MRI) data. Finite element analysis was performed to acquire six different dilated CoAs. The unsteady pulsatile flow was resolved by large eddy simulation (LES) including non-Newtonian blood rheology. Pre-intervention, the presence of jet flow wall impingement caused an elevated WSS zone, with a distal region of low and oscillatory WSS. After intervention, cases with a more favorable centralized jet showed reduced high WSS values at the opposed wall. Despite significant turbulence reduction post-treatment, enhanced regions of low and oscillatory WSS were observed for all cases. This numerical method has demonstrated the morphological impact on WSS distribution in an CoA. With the predictability and validation capabilities of a combined CFD/MRI approach, a step towards patient-specific intervention planning is taken.

  16. Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2010-01-01

    Full Text Available Background/Aim. The main complication of the atherosclerotic abdominal aortic aneurism (AAA is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. Method. During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 μm thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff - PAS stain and immunocytochemically using a DAKO LSAB+/HRP technique to identify α-smooth muscle actin (α-SMA, vimentin, myosin heavy chains (MHC, desmin, S-100 protein, CD45 and CD68 (DAKO specification. Results. The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs are present, which express a α-SMA and vimentin (but without MHC or desmin expression, as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68-immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection. Conclusion. Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the

  17. 3-D segmentation and quantitative analysis of inner and outer walls of thrombotic abdominal aortic aneurysms

    Science.gov (United States)

    Lee, Kyungmoo; Yin, Yin; Wahle, Andreas; Olszewski, Mark E.; Sonka, Milan

    2008-03-01

    An abdominal aortic aneurysm (AAA) is an area of a localized widening of the abdominal aorta, with a frequent presence of thrombus. A ruptured aneurysm can cause death due to severe internal bleeding. AAA thrombus segmentation and quantitative analysis are of paramount importance for diagnosis, risk assessment, and determination of treatment options. Until now, only a small number of methods for thrombus segmentation and analysis have been presented in the literature, either requiring substantial user interaction or exhibiting insufficient performance. We report a novel method offering minimal user interaction and high accuracy. Our thrombus segmentation method is composed of an initial automated luminal surface segmentation, followed by a cost function-based optimal segmentation of the inner and outer surfaces of the aortic wall. The approach utilizes the power and flexibility of the optimal triangle mesh-based 3-D graph search method, in which cost functions for thrombus inner and outer surfaces are based on gradient magnitudes. Sometimes local failures caused by image ambiguity occur, in which case several control points are used to guide the computer segmentation without the need to trace borders manually. Our method was tested in 9 MDCT image datasets (951 image slices). With the exception of a case in which the thrombus was highly eccentric, visually acceptable aortic lumen and thrombus segmentation results were achieved. No user interaction was used in 3 out of 8 datasets, and 7.80 +/- 2.71 mouse clicks per case / 0.083 +/- 0.035 mouse clicks per image slice were required in the remaining 5 datasets.

  18. Proteins associated with the size and expansion rate of the abdominal aortic aneurysm wall as identified by proteomic analysis

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Lindholt, Jes S.; Delbosc, Sandrine

    2010-01-01

    Identification of biomarkers for the natural history of abdominal aortic aneurysms (AAA) holds the key to non-surgical intervention and improved selection for AAA repair. We aimed to associate the basic proteomic composition of AAA wall tissue with the expansion rate and size in patients with AAA....

  19. The presence of fructosamine in human aortic valves is associated with valve stiffness.

    Science.gov (United States)

    Kishabongo, Antoine S; Katchunga, Philippe; Cikomola, Justin C; De Somer, Filip M; De Buyzere, Marc L; Speeckaert, Marijn M; Delanghe, Joris R

    2016-09-01

    Human heart valves are prone to glycation, a fundamental process of ageing. The aim of this study was to establish the relationship between fructosamine formation and the mechanical properties of human aortic valves. 67 patients (age: 76±8 years) diagnosed with an aortic valve stenosis, who underwent an aortic valve replacement were enrolled. Fructosamine and calcium concentrations in aortic valves were determined. Using a transthoracic Doppler echocardiography, aortic valve orifice area and transvalvular pressure gradients were measured. In a subgroup of 32 patients, the aortic valve orifice area was sufficient to carry out mechanical testing on a LFPlus Universal material tester. An in vitro removal of fructosamine of the valve was initiated using ATP-dependent fructosamine 3-kinase (FN3K). A significant correlation was found between the aortic valve fructosamine concentration and the calculated aortic valve orifice area: Y (aortic valve orifice area, mm(2))=1.050-0.228X (aortic valve fructosamine concentration, µmol/g valve) (r=-0.38). A significantly higher calcium concentration was measured in the aortic valves of diabetics in comparison with those of non-diabetics. A multiple regression analysis revealed that the presence of diabetes mellitus and aortic valve fructosamine concentration were the main predictors of the extensibility of the aortic valves. In the in vitro deglycation study, a significant lower aortic valve fructosamine concentration was detected after treatment with FN3K. This resulted in an increased flexibility of the aortic valves. Although no direct causativeness is proven with the presented results, which just show an association between fructosamine, the effect of FN3K and aortic valve stiffness, the present study points for the first time towards a possible additional role of the Amadori products in the biomechanical properties of ageing aortic valves. Published by the BMJ Publishing Group Limited. For permission to use (where not

  20. Nanostructure of Human Aortic Intima in Atherosclerosis (A Pilot Study

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    A. M. Golubev

    2016-01-01

    Full Text Available Objective: to analyze the nanostructure of human aortic intima in atherosclerosis and demonstrate the poten tial effect of Niodex on cholesterol plaques.Materials and methods. Samples of intima were taken from those parts of aorta, where different stages of atherosclerotic chages were obvious. Aortic samples were incubated in a solution containing cyclodextrins. A solution of NIODEX, a propylene glycol ester of betacyclodextrin, was used in the study. A layer of aortic intima was formed on the glass slide surface with polylysine. The samples were placed into the working area of an atomicforce microscope (Integra Prima, NTMDT, Russian Federation, and their surfaces were scanned. The number of imaging points was 512; and the imaging regions were as follows: 100100 μm, 20002000 nm.Results. Classification of nanosurface objects was performed and typical fragments (craters, ridges, and trabecular fibers were identified, and quantitative assessment of their sizes was carried out. 27 fragments were identified as growing cholesterol plaques. 16 of them measuring 900—1200 nm were identified near ridges, and 11 near craters (600—1050 nm. Niodex caused destruction of lipid spots and smoothing of the intima surface. More than a half of the 27 identified objects (15 demostrated a 30% and more decrease in size (median 340—400 nm. A 10—15% decrease was registered in 7 fragments; in the remaining 5 fragments, the decrease in the lesion size was less than 10%.Conclusion. Raw data permit to suppose that the effect of Niodex on the aortic intima results in decceleartion and decreased intensity of atherosclerotic plaque growth on the intima fragments.

  1. Self-gated CINE MRI for combined contrast-enhanced imaging and wall-stiffness measurements of murine aortic atherosclerotic lesions.

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    Brigit den Adel

    Full Text Available BACKGROUND: High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent. METHODS AND RESULTS: We applied a 2D-FLASH retrospective-gated CINE MRI method at 9.4T to characterize atherosclerotic plaques and vessel wall distensibility in the aortic arch of aged ApoE(-/- mice after injection of a contrast agent. The method enabled detection of contrast enhancement in atherosclerotic plaques in the aortic arch after I.V. injection of micelles and iron oxides resulting in reproducible plaque enhancement. Both contrast agents were taken up in the plaque, which was confirmed by histology. Additionally, the retrospective-gated CINE method provided images of the aortic wall throughout the cardiac cycle, from which the vessel wall distensibility could be calculated. Reduction in plaque size by statin treatment resulted in lower contrast enhancement and reduced wall stiffness. CONCLUSIONS: The retrospective-gated CINE MRI provides a robust and simple way to detect and quantify contrast enhancement in atherosclerotic plaques in the aortic wall of ApoE(-/- mice. From the same scan, plaque-related changes in stiffness of the aortic wall can be determined. In this mouse model, a correlation between vessel wall stiffness and atherosclerotic lesions was found.

  2. Aortic dissection (image)

    Science.gov (United States)

    Aortic dissection is a condition in which there is bleeding into and along the wall of the aorta (the ... the inner wall of the artery. Although aortic dissection can affect anybody, it is most often seen ...

  3. Single-walled carbon nanotubes (SWCNTs) induce vasodilation in isolated rat aortic rings.

    Science.gov (United States)

    Gutiérrez-Hernández, J M; Ramirez-Lee, M A; Rosas-Hernandez, H; Salazar-García, S; Maldonado-Ortega, D A; González, F J; Gonzalez, C

    2015-06-01

    Single-walled carbon nanotubes (SWCNTs) are used in biological systems with impact in biomedicine in order to improve diagnostics and treatment of diseases. However, their effects upon the vascular system, are not fully understood. Endothelium and smooth muscle cells (SMC) communicate through release of vasoactive factors as nitric oxide (NO) to maintain vascular tone. The aim of this study was to evaluate the effect of SWCNTs on vascular tone using isolated rat aortic rings, which were exposed to SWCNTs (0.1, 1 and 10 μg/mL) in presence and absence of endothelium. SWCNTs induced vasodilation in both conditions, indicating that this effect was independent on endothelium; moreover that vasodilation was NO-independent, since its blockage with L-NAME did not modify the observed effect. Together, these results indicate that SWCNTs induce vasodilation in the macrovasculature, may be through a direct interaction with SMC rather than endothelium independent of NO production. Further investigation is required to fully understand the mechanisms of action and mediators involved in the signaling pathway induced by SWCNTs on the vascular system.

  4. 3D Computer Simulations of Pulsatile Human Blood Flows in Vessels and in the Aortic Arch: Investigation of Non-Newtonian Characteristics of Human Blood

    CERN Document Server

    Sultanov, Renat A; Engelbrekt, Brent; Blankenbecler, Richard

    2008-01-01

    Methods of Computational Fluid Dynamics are applied to simulate pulsatile blood flow in human vessels and in the aortic arch. The non-Newtonian behaviour of the human blood is investigated in simple vessels of actual size. A detailed time-dependent mathematical convergence test has been carried out. The realistic pulsatile flow is used in all simulations. Results of computer simulations of the blood flow in vessels of two different geometries are presented. For pressure, strain rate and velocity component distributions we found significant disagreements between our results obtained with realistic non-Newtonian treatment of human blood and widely used method in literature: a simple Newtonian approximation. A significant increase of the strain rate and, as a result, wall sear stress distribution, is found in the region of the aortic arch. We consider this result as theoretical evidence that supports existing clinical observations and those models not using non-Newtonian treatment underestimate the risk of disru...

  5. Genetic and Epigenetic Regulation of Aortic Aneurysms

    Science.gov (United States)

    Kim, Ha Won

    2017-01-01

    Aneurysms are characterized by structural deterioration of the vascular wall leading to progressive dilatation and, potentially, rupture of the aorta. While aortic aneurysms often remain clinically silent, the morbidity and mortality associated with aneurysm expansion and rupture are considerable. Over 13,000 deaths annually in the United States are attributable to aortic aneurysm rupture with less than 1 in 3 persons with aortic aneurysm rupture surviving to surgical intervention. Environmental and epidemiologic risk factors including smoking, male gender, hypertension, older age, dyslipidemia, atherosclerosis, and family history are highly associated with abdominal aortic aneurysms, while heritable genetic mutations are commonly associated with aneurysms of the thoracic aorta. Similar to other forms of cardiovascular disease, family history, genetic variation, and heritable mutations modify the risk of aortic aneurysm formation and provide mechanistic insight into the pathogenesis of human aortic aneurysms. This review will examine the relationship between heritable genetic and epigenetic influences on thoracic and abdominal aortic aneurysm formation and rupture. PMID:28116311

  6. Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Tsutsui, H.; Tomoike, H.; Nakamura, M. (Kyushu Univ., Fukuoka (Japan))

    1990-08-01

    Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using ({sup 14}C)antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of ({sup 14}C)antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.

  7. Comparative in Vitro Research of the Human Aortic Bioprosthesis

    Directory of Open Access Journals (Sweden)

    Dawidowska K.

    2014-12-01

    Full Text Available Evaluate of the usefulness and reliability of structures based on the analysis of recorded parameters determining the flow through the Human Aortic Bioprosthesis (HAB have been dealt with. By flow parameters changes determining the performance environment of prosthesis analyzed change of the motion dynamics of the valve leaflets as a function of pressure, thereby determining the degree of alignment of the prosthesis to the performance conditions. Based on the gathered measurement data a comparative analysis of flow rate valve prostheses for different frequency values of the piston pump imitating the heart, different ejection capacity and pressure conditioning work environment prosthesis were studied. Interpretation of the recorded image gave the basis for determining the Effective Orifice Area (EOC.

  8. Quantifying turbulent wall shear stress in a subject specific human aorta using large eddy simulation.

    Science.gov (United States)

    Lantz, Jonas; Gårdhagen, Roland; Karlsson, Matts

    2012-10-01

    In this study, large-eddy simulation (LES) is employed to calculate the disturbed flow field and the wall shear stress (WSS) in a subject specific human aorta. Velocity and geometry measurements using magnetic resonance imaging (MRI) are taken as input to the model to provide accurate boundary conditions and to assure the physiological relevance. In total, 50 consecutive cardiac cycles were simulated from which a phase average was computed to get a statistically reliable result. A decomposition similar to Reynolds decomposition is introduced, where the WSS signal is divided into a pulsating part (due to the mass flow rate) and a fluctuating part (originating from the disturbed flow). Oscillatory shear index (OSI) is plotted against time-averaged WSS in a novel way, and locations on the aortic wall where elevated values existed could easily be found. In general, high and oscillating WSS values were found in the vicinity of the branches in the aortic arch, while low and oscillating WSS were present in the inner curvature of the descending aorta. The decomposition of WSS into a pulsating and a fluctuating part increases the understanding of how WSS affects the aortic wall, which enables both qualitative and quantitative comparisons.

  9. Human tissue valves in aortic position: determinants of reoperation and valve regurgitation

    NARCIS (Netherlands)

    T.P. Willems (Tineke); E.W. Steyerberg (Ewout); V.E. Kleyburg-Linkers; E. Bos (Egbert); L.A. van Herwerden (Lex); J.R.T.C. Roelandt (Jos); J.J.M. Takkenberg (Hanneke)

    2001-01-01

    textabstractBACKGROUND: Human tissue valves for aortic valve replacement have a limited durability that is influenced by interrelated determinants. Hierarchical linear modeling was used to analyze the relation between these determinants of durability and valve

  10. EXPRESSION OF MATRIX METALLOPROTEINASE-9 IN HUMAN ABDOMINAL AORTIC ANEURYSMAL TISSUES

    Institute of Scientific and Technical Information of China (English)

    Ma Zhong; Wang Ling; Qi Guangyu; Joerg. Heckenkamp

    2006-01-01

    Objective To study the effects of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the pathogenesis of abdominal aortic aneurysms (AAAs) by localizing the expression of MMP-9 in the aneurysmal tissues. Methods By means of immunohistochemistry, the frozen sections (5 μm) with aneurysmal tissues (n = 10) were incubated with MMP-9 antibody-added agents, then the sections were stained and observed under the microscope to localize the expression of MMP-9, which displayed a brown precipitate within the arterial walls. The normal arterial wall tissues(n= 10)and the diseased arterial wall tissues from the arterial occlusive diseases (AODs) (n= 15) were also immunized exactly the same way as control. Results A quantity of positive granules which appeared within the aortic media showed the strong expression of MMP-9 in the AAAs, with the positive rate reaching 95%(19/20), while no expression of MMP-9 was observed in the normal artery. However, the scattered distributed positive granules were scen within the arterial wall of some cases of the AODs, implying the weak positive expression of MMP-9 in this disease with the positive rate of 26.7%(4/15). There was a significant difference of the expression of MMP-9 within the arterial wall between the AAAs and AODs(P<0. 01). Conclusion High expression of MMP-9 within the aortic media faciliatates the degradation of collagen and elastin fibres and subsequent dilation of the aortic artery , thus playing an important role in the pathogenesis of AAAs. To refrain MMP-9 from enhanced expressing within the aortic wall is of clinical significance in the prevention and treatment of AAAs.

  11. Embolic capture with updated intra-aortic filter during coronary artery bypass grafting and transaortic transcatheter aortic valve implantation: first-in-human experience.

    Science.gov (United States)

    Ye, Jian; Webb, John G

    2014-12-01

    We report our first-in-human clinical experience in the use of the new version of the EMBOL-X intra-aortic filter (Edwards Lifesciences Corporation, Irvine, Calif) to capture embolic material during transaortic transcatheter aortic valve implantation and cardiac surgery. Five patients were enrolled into the first-in-human clinical assessment of the new version of the EMBOL-X intra-aortic filter. Three patients underwent coronary artery bypass grafting, and 2 patients underwent transaortic transcatheter aortic valve implantation. During coronary artery bypass grafting, the filter was deployed before clamping of the aorta and removal of the aortic clamp. In contrast, the filter was deployed before aortic puncture for transaortic transcatheter aortic valve implantation and kept in the aorta throughout the entire procedure. The filter introducer sheath and filter were easily placed and removed without difficulty. There were no complications related to the use of the filter. Postoperative examination of the retrieved filters revealed the presence of multiple microemboli in the filters from all 5 cases. Histologic study revealed various kinds of tissue and thrombus. This first-in-human clinical experience has demonstrated the safety and feasibility of using the new version of the EMBOL-X intra-aortic filter during either cardiac surgery or transaortic transcatheter aortic valve implantation. We believe that the combination of the transaortic approach without aortic arch manipulation and the use of the EMBOL-X filter with a high capture rate is a promising strategy to reduce the incidence of embolic complications during transcatheter aortic valve implantation. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  12. Converting enzyme inhibitor temocaprilat prevents high glucose-mediated suppression of human aortic endothelial cell proliferation.

    Science.gov (United States)

    Yasunari, Kenichi; Maeda, Kensaku; Watanabe, Takanori; Nakamura, Munehiro; Asada, Akira; Yoshikawa, Junichi

    2003-12-01

    We examined the involvement of the oxidative stress in high glucose-induced suppression of human aortic endothelial cell proliferation. Chronic glucose treatment for 72 h concentration-dependently (5.6-22.2 mol/l) inhibited human coronary endothelial cell proliferation. Temocaprilat, an angiotensin-converting enzyme inhibitor, at 10 nmol/l to 1 micromol/l inhibited high glucose (22.2 mmol/l)-mediated suppression of human aortic endothelial cell proliferation. Temocaprilat at 1 micromol/l inhibited high glucose-induced membrane-bound protein kinase C activity in human aortic endothelial cells. The protein kinase C inhibitors calphostin C 100 nmol/l or chelerythrine 1 micromol/l inhibited high glucose-mediated suppression of human aortic endothelial cell proliferation. Chronic high glucose treatment for 72 h increased intracellular oxidative stress, directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by temocaprilat 10 nmol/l to 1 micromol/l. Bradykinin B2 receptor antagonist icatibant 100 nmol/l significantly reduced the action of temocaprilat; whereas bradykinin B1 receptor antagonist des-Arg9-Leu8-bradykinin 100 nmol/l had no effect. These findings suggest that high glucose inhibits human aortic endothelial cell proliferation and that the angiotensin-converting enzyme inhibitor temocaprilat inhibits high glucose-mediated suppression of human aortic endothelial cell proliferation, possibly through suppression of protein kinase C, bradykinin B2 receptors and oxidative stress.

  13. Aortic Valve Disease

    Science.gov (United States)

    ... Tricuspid Valve Disease Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Pediatric and Congenital Heart Disease Heart abnormalities that are ... Transplantation End-stage Lung Disease Adult Lung Transplantation Pediatric Lung ... Aortic Aneurysm Aortic Valve Disease Overview The human heart has ...

  14. Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm doxycycline selectively depletes aortic wall neutrophils and cytotoxic t cells

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Bockel, J.H. van; Wolterbeek, R.; Kleemann, R.

    2009-01-01

    Background-Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies. We reevaluated the effect of doxycycline on aortic wal

  15. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.

    Science.gov (United States)

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N; Hascall, Vincent C; De Luca, Giancarlo; Passi, Alberto

    2013-10-11

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.

  16. Asthma Associates With Human Abdominal Aortic Aneurysm and Rupture

    DEFF Research Database (Denmark)

    Liu, Cong-Lin; Wemmelund, Holger; Wang, Yi

    2016-01-01

    OBJECTIVE: Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact. APPROACH AND RESULTS: Databases analyzed included Danish National Registry of Patients, a population-based nationwide case-control study included all patients...

  17. Relation of aortic calcification, wall thickness, and distensibility with severity of coronary artery disease: evaluation with coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Seonah; Yong, Hwan Seok; Doo, Kyung Won; Kang, Eun-Young; Woo, Ok Hee; Choi, Eun Jung [Dept. of Radiology, Korea Univ. Guro Hospital, Korea Univ. College of Medicine, Seoul (Korea, Republic of)], e-mail: yhwanseok@naver.com

    2012-10-15

    Background Three known risk factors for aortic atherosclerosis predict the severity of coronary artery disease (CAD): aortic calcification (AC), aortic wall thickness (AWT), and aortic distensibility (AD). Purpose To determine the relationship of AC, AWT, and AD with the severity of CAD. Material and Methods A total of 104 patients who underwent both coronary CT angiography (CCTA) and invasive coronary angiography were enrolled. The severity of CAD was assessed by three methods: the segment involvement score (SIS), the segment stenosis score (SSS), and the modified Gensini score (mG). We quantified AC using the Agatston method on low-dose ungated chest CT (LDCT). We measured AWT at the thickest portion of the descending thoracic aorta on CCTA. AD was calculated as the difference between the maximum and minimum areas of the ascending aorta and the pulse pressure. The relationships between the severity of CAD and the three aortic factors were assessed. Results The AC and AWT of the thoracic aorta were significantly higher in the occlusive CAD (OCAD) group (1984.21 {+-} 2986.10 vs. 733.00 {+-} 1648.71, P = 0.01; 4.13 {+-} 1.48 vs. 3.40 {+-} 1.01, P = 0.22). Patients with OCAD had more than one epicardial coronary artery with >50% luminal stenosis. The AC (r = 0.453 with SIS; r = 0.454 with SSS; r = 0.427 with mG) and the AWT (r = 0.279 with SIS; r = 0.324 with SSS; r = 0.304 with mG) were significantly correlated with all three methods, and the AD was negatively correlated with the SIS (r = - 0.221, P < 0.05, respectively) in the unadjusted model. After adjustment for cardiovascular risk factors, only the correlations between AC and all three methods assessing CAD remained significant. Conclusion There are significant relationships between AC, AWT and AD and severity of CAD. In particular, AC measured on LDCT is the most consistent predictor of severity of CAD.

  18. Association of aortic wall thickness on contrast-enhanced chest CT with major cerebro-cardiac events.

    Science.gov (United States)

    Tresoldi, Silvia; Di Leo, Giovanni; Zoffoli, Elena; Munari, Alice; Primolevo, Alessandra; Cornalba, Gianpaolo; Sardanelli, Francesco

    2014-11-01

    There is a significant association between aortic atherosclerosis and previous major cardiovascular events. Particularly, thoracic aortic atherosclerosis is closely related to the degree of coronary and carotid artery disease. Thus, there is a rationale for screening the thoracic aorta in patients who undergo a chest computed tomography (CT) for any clinical question, in order to detect patients at increased risk of cerebro-cardiovascular (CCV) events. To estimate the association between either thoracic aortic wall thickness (AWT) or aortic total calcium score (ATCS) and CCV events. One hundred and forty-eight non-cardiac patients (78 men; 67 ± 12 years) underwent chest contrast-enhanced multidetector CT (MDCT). The AWT was measured at the level of the left atrium (AWTref) and at the maximum AWT (AWTmax). Correlation with clinical CCV patients' history was estimated. The value of AWTmax and of a semi-quantitative ATCS as a marker for CCV events was assessed using receiver-operating characteristic curve (ROC) analysis and multivariate regression analysis. Out of 148 patients, 59% reported sedentary lifestyle, 44% hypertension, 32% smoking, 23% hypercholesterolemia, 13% family history of cardiac disease, 12% diabetes, and 10% BMI ≥ 30 kg/m(2); 9% reported myocardial infarction, 8% aortic aneurism, 8% myocardial revascularization, and 2% ischemic stroke. Twenty-six percent of patients had a medium-to-high ATCS. Both AWTmax and AWTref correlated with hypertension and age (P < 0.002). At the ROC analysis, a 4.8 mm threshold was associated to a 90% specificity and an odds ratio of 6.3 (AUC = 0.735). Assuming as threshold the AWTmax median value (4.3 mm) of patients who suffered from at least one CCV event in their history, a negative predictive value of 90%, a RR of 3.6 and an OR of 6.3 were found. At the multivariate regression analysis, AWTmax was the only independent variable associated to the frequency of CCV events. Patients with increased thoracic

  19. Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms.

    Science.gov (United States)

    Grigoryants, Vladimir; Hannawa, Kevin K; Pearce, Charles G; Sinha, Indranil; Roelofs, Karen J; Ailawadi, Gorav; Deatrick, Kristopher B; Woodrum, Derek T; Cho, Brenda S; Henke, Peter K; Stanley, James C; Eagleton, Matthew J; Upchurch, Gilbert R

    2005-01-01

    controls on day 7 (P = .05). Administration of the direct catalase inhibitor AT to tamoxifen-treated rats partially reversed the aneurysm inhibitory effect of tamoxifen by nearly 30% (P = .02). In contrast, catalase administration inhibited AAA formation by 44% (P = .002). The selective estrogen receptor modulator tamoxifen inhibits the development of AAAs in male rats in association with an up-regulation of catalase and inhibition of aortic wall neutrophil infiltration.

  20. Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

    Science.gov (United States)

    Tantawy, Azza A G; Adly, Amira A M; Ismail, Eman A R; Habeeb, Nevin M

    2013-06-01

    Heart disease is the leading cause of mortality and morbidity in β-thalassemia major (β-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young β-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P 2500 μg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

  1. Characterization of human aortic elastase found in patients with abdominal aortic aneurysms.

    Science.gov (United States)

    Cohen, J R; Mandell, C; Wise, L

    1987-10-01

    Recent evidence indicates that the homeostatic balance between elastase and antiprotease activity is altered in the infrarenal aorta of those patients with different types of aortic pathologic findings. The specific properties of elastase found in the aorta of patients with abdominal aortic aneurysms (AAA) are discussed herein. Activity of elastase extracted from ten pooled AAA specimens was observed when incubated with several inhibitors: 13.2 per cent for phenyl-suphonyl flouride (PSF); 43.3 per cent for ethylenediaminetetraacetic acid (EDTA); 77.7 per cent for pepstatin; 137.0 per cent for leupeptin, and 24.0 per cent for alpha-1-antitrypsin. Irreversible inhibition by PSF indicates that the elastase is a serine protease. The elastase is most likely not a metallo enzyme, since it had no absolute requirement for divalent cations as indicated by only partial inhibition by EDTA. Elastase activity is most likely not due to cathepsins B or D, since cathepsins are active in an acid pH and selectively inhibited by leupeptin and pepstatin. The pH curve revealed a maximum activity at pH 8.2 and elastase activity was significantly inhibited by alpha-1-antitrypsin in a dose response manner determining functional elastase activity. These data indicate that the elastase in the aorta of patients with an AAA has the exact properties of the serine elastase found in the smooth muscle cells of the aorta in rats. These results also confirm the critical role of alpha-1-antitrypsin in determining functional elastase activity. Smooth muscle cell regulation of elastin metabolism may be important in determining why some patients have AAA and others have occlusive aortic disease develop.

  2. Development of the human aortic arch system captured in an interactive three-dimensional reference model.

    Science.gov (United States)

    Rana, M Sameer; Sizarov, Aleksander; Christoffels, Vincent M; Moorman, Antoon F M

    2014-06-01

    Variations and mutations in the human genome, such as 22q11.2 microdeletion, can increase the risk for congenital defects, including aortic arch malformations. Animal models are increasingly expanding our molecular and genetic insights into aortic arch development. However, in order to justify animal-to-human extrapolations, a human morphological, and molecular reference model would be of great value, but is currently lacking. Here, we present interactive three-dimensional reconstructions of the developing human aortic arch system, supplemented with the protein distribution of developmental markers for patterning and growth, including T-box transcription factor TBX1, a major candidate for the phenotypes found in patients with the 22q11.2 microdeletion. These reconstructions and expression data facilitate unbiased interpretations, and reveal previously unappreciated aspects of human aortic arch development. Based on our reconstructions and on reported congenital anomalies of the pulmonary trunk and tributaries, we postulate that the pulmonary arteries originate from the aortic sac, rather than from the sixth pharyngeal arch arteries. Similar to mouse, TBX1 is expressed in pharyngeal mesenchyme and epithelia. The endothelium of the pharyngeal arch arteries is largely negative for TBX1 and family member TBX2 but expresses neural crest marker AP2α, which gradually decreases with ongoing development of vascular smooth muscle. At early stages, the pharyngeal arch arteries, aortic sac, and the dorsal aortae in particular were largely negative for proliferation marker Ki67, potentially an important parameter during aortic arch system remodeling. Together, our data support current animal-to-human extrapolations and future genetic and molecular analyses using animal models of congenital heart disease. © 2013 Wiley Periodicals, Inc.

  3. Prostanoid Receptors in the Human Vascular Wall

    Directory of Open Access Journals (Sweden)

    Xavier Norel

    2007-01-01

    Full Text Available The mechanisms involved in vascular homeostasis and disease are mostly dependent on the interactions between blood, vascular smooth muscle, and endothelial cells. There is an accumulation of evidence for the involvement of prostanoids, the arachidonic acid metabolites derived from the cyclooxygenase enzymatic pathway, in physiological and/or pathophysiological conditions. In humans, the prostanoids activate different receptors. The classical prostanoid receptors (DP, EP1–4, FP, IP, and TP are localized at the cell plasma or nuclear membrane. In addition, CRTH2 and the nuclear PPAR receptors are two other targets for prostanoids, namely, prostacyclin (PGI2 or the natural derivatives of prostaglandin D2. While there is little information on the role of CRTH2, there are many reports on PPAR activation and the consecutive expression of genes involved in the human vascular system. The role of the classical prostanoid receptors stimulated by PGI2 and thromboxane in the control of the vascular tone has been largely documented, whereas the other receptor subtypes have been overlooked. There is now increasing evidence that suggests a role of PGE2 and the EP receptor subtypes in the control of the human vascular tone and remodeling of the vascular wall. These receptors are also present on leukocytes and platelets, and they are implicated in most of the inflammatory processes within the vascular wall. Consequently, the EP receptor subtypes or isoforms would provide a novel and specific cardiovascular therapeutic approach in the near future.

  4. Modified lipoprotein-derived lipid particles accumulate in human stenotic aortic valves.

    Science.gov (United States)

    Lehti, Satu; Käkelä, Reijo; Hörkkö, Sohvi; Kummu, Outi; Helske-Suihko, Satu; Kupari, Markku; Werkkala, Kalervo; Kovanen, Petri T; Oörni, Katariina

    2013-01-01

    In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine -ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis.

  5. RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing.

    Science.gov (United States)

    Guauque-Olarte, Sandra; Droit, Arnaud; Tremblay-Marchand, Joël; Gaudreault, Nathalie; Kalavrouziotis, Dimitri; Dagenais, Francois; Seidman, Jonathan G; Body, Simon C; Pibarot, Philippe; Mathieu, Patrick; Bossé, Yohan

    2016-10-01

    The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.

  6. Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

    Science.gov (United States)

    Zeng, Qingchun; Song, Rui; Fullerton, David A.; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B.; Cleveland, Joseph C.; Reece, T. Brett; McKinsey, Timothy A.; Xu, Dingli; Dinarello, Charles A.; Meng, Xianzhong

    2017-01-01

    Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease. PMID:28137840

  7. Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells.

    Science.gov (United States)

    Schramm, D D; Wang, J F; Holt, R R; Ensunsa, J L; Gonsalves, J L; Lazarus, S A; Schmitz, H H; German, J B; Keen, C L

    2001-01-01

    Polyphenolic phytochemicals inhibit vascular and inflammatory processes that contribute to disease. These effects are hypothesized to result from polyphenol-mediated alterations in cellular eicosanoid synthesis. The objective was to determine and compare the ability of cocoa procyanidins to alter eicosanoid synthesis in human subjects and cultured human aortic endothelial cells. After an overnight fast, 10 healthy subjects (4 men and 6 women) consumed 37 g low-procyanidin (0.09 mg/g) and high-procyanidin (4.0 mg/g) chocolate; the treatments were separated by 1 wk. The investigation had a randomized, blinded, crossover design. Plasma samples were collected before treatment and 2 and 6 h after treatment. Eicosanoids were quantitated by enzyme immunoassay. Endothelial cells were treated in vitro with procyanidins to determine whether the effects of procyanidin in vivo were associated with procyanidin-induced alterations in endothelial cell eicosanoid synthesis. Relative to the effects of the low-procyanidin chocolate, high-procyanidin chocolate induced increases in plasma prostacyclin (32%; P<0.05) and decreases in plasma leukotrienes (29%; P<0.04). After the in vitro procyanidin treatments, aortic endothelial cells synthesized twice as much 6-keto-prostaglandin F(1alpha) (P<0.01) and 16% less leukotriene (P<0.05) as did control cells. The in vitro and in vivo effects of procyanidins on plasma leukotriene-prostacyclin ratios in culture medium were also comparable: decreases of 58% and 52%, respectively. Data from this short-term investigation support the concept that certain food-derived flavonoids can favorably alter eicosanoid synthesis in humans, providing a plausible hypothesis for a mechanism by which they can decrease platelet activation in humans.

  8. Aortic dissection

    Science.gov (United States)

    Aortic aneurysm - dissecting; Chest pain - aortic dissection; Thoracic aortic aneurysm - dissection ... the chest and abdomen (the descending aorta). Aortic dissection most often happens because of a tear or ...

  9. Three-dimensional macro-scale assessment of regional and temporal wall shear stress characteristics on aortic valve leaflets.

    Science.gov (United States)

    Cao, K; Bukač, M; Sucosky, P

    2016-01-01

    The aortic valve (AV) achieves unidirectional blood flow between the left ventricle and the aorta. Although hemodynamic stresses have been shown to regulate valvular biology, the native wall shear stress (WSS) experienced by AV leaflets remains largely unknown. The objective of this study was to quantify computationally the macro-scale leaflet WSS environment using fluid-structure interaction modeling. An arbitrary Lagrangian-Eulerian approach was implemented to predict valvular flow and leaflet dynamics in a three-dimensional AV geometry subjected to physiologic transvalvular pressure. Local WSS characteristics were quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI) and temporal shear gradient (TSG). The dominant radial WSS predicted on the leaflets exhibited high amplitude and unidirectionality on the ventricularis (TSM>7.50 dyn/cm(2), OSI 325.54 dyn/cm(2) s) but low amplitude and bidirectionality on the fibrosa (TSM 0.38, TSG 0.25). This study provides new insights into the role played by leaflet-blood flow interactions in valvular function and critical hemodynamic stress data for the assessment of the hemodynamic theory of AV disease.

  10. Cross Talk between NOTCH Signaling and Biomechanics in Human Aortic Valve Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Richard C. Godby

    2014-12-01

    Full Text Available Aortic valve disease is a burgeoning public health problem associated with significant mortality. Loss of function mutations in NOTCH1 cause bicuspid aortic valve (BAV and calcific aortic valve disease. Because calcific nodules manifest on the fibrosa side of the cusp in low fluidic oscillatory shear stress (OSS, elucidating pathogenesis requires approaches that consider both molecular and mechanical factors. Therefore, we examined the relationship between NOTCH loss of function (LOF and biomechanical indices in healthy and diseased human aortic valve interstitial cells (AVICs. An orbital shaker system was used to apply cyclic OSS, which mimics the cardiac cycle and hemodynamics experienced by AVICs in vivo. NOTCH LOF blocked OSS-induced cell alignment in human umbilical vein endothelial cells (HUVECs, whereas AVICs did not align when subjected to OSS under any conditions. In healthy AVICs, OSS resulted in decreased elastin (ELN and α-SMA (ACTA2. NOTCH LOF was associated with similar changes, but in diseased AVICs, NOTCH LOF combined with OSS was associated with increased α-SMA expression. Interestingly, AVICs showed relatively higher expression of NOTCH2 compared to NOTCH1. Biomechanical interactions between endothelial and interstitial cells involve complex NOTCH signaling that contributes to matrix homeostasis in health and disorganization in disease.

  11. Free-breathing black-blood CINE fast-spin echo imaging for measuring abdominal aortic wall distensibility: a feasibility study

    Science.gov (United States)

    Lin, Jyh-Miin; Patterson, Andrew J.; Chao, Tzu-Cheng; Zhu, Chengcheng; Chang, Hing-Chiu; Mendes, Jason; Chung, Hsiao-Wen; Gillard, Jonathan H.; Graves, Martin J.

    2017-05-01

    The paper reports a free-breathing black-blood CINE fast-spin echo (FSE) technique for measuring abdominal aortic wall motion. The free-breathing CINE FSE includes the following MR techniques: (1) variable-density sampling with fast iterative reconstruction; (2) inner-volume imaging; and (3) a blood-suppression preparation pulse. The proposed technique was evaluated in eight healthy subjects. The inner-volume imaging significantly reduced the intraluminal artifacts of respiratory motion (p  =  0.015). The quantitative measurements were a diameter of 16.3  ±  2.8 mm and wall distensibility of 2.0  ±  0.4 mm (12.5  ±  3.4%) and 0.7  ±  0.3 mm (4.1  ±  1.0%) for the anterior and posterior walls, respectively. The cyclic cross-sectional distensibility was 35  ±  15% greater in the systolic phase than in the diastolic phase. In conclusion, we developed a feasible CINE FSE method to measure the motion of the abdominal aortic wall, which will enable clinical scientists to study the elasticity of the abdominal aorta.

  12. Free-breathing black-blood CINE fast-spin echo imaging for measuring abdominal aortic wall distensibility: A feasibility study.

    Science.gov (United States)

    Lin, Jyh-Miin; Patterson, Andrew; Chao, Tzu-Cheng; Zhu, Chengcheng; Chang, Hing-Chiu; Mendes, Jason; Chung, Hsiao-Wen; Gillard, Jonathan; Graves, Martin

    2017-03-22

    The paper reports a free-breathing black-blood CINE fast-spin echo (FSE) technique for measuring abdominal aortic wall motion. The free-breathing CINE FSE includes the following MR techniques: 1) variable-density sampling with fast iterative reconstruction; 2) inner-volume imaging; and 3) a blood-suppression preparation pulse. The proposed technique was evaluated in eight healthy subjects. The inner-volume imaging significantly reduced the intraluminal artifacts of respiratory motion (p = 0.015). The quantitative measurements were a diameter of 16.3 ± 2.8 mm and wall distensibility of 2.0 ± 0.4 mm (12.5 ± 3.4%) and 0.7 ± 0.3 mm (4.1 ± 1.0%) for the anterior and posterior walls, respectively. The cyclic cross-sectional distensibility was 35 ± 15% greater in the systolic phase than in the diastolic phase. In conclusion, we developed a feasible CINE FSE method to measure the motion of the abdominal aortic wall, which will enable clinical scientists to study the elasticity of the abdominal aorta.

  13. Transitional features in human atherosclerosis. Intimal thickening, cholesterol clefts, and cell loss in human aortic fatty streaks.

    OpenAIRE

    Guyton, J. R.; Klemp, K. F.

    1993-01-01

    The possible transition from a subset of fatty streaks to fibrous plaques in human atherosclerosis has long been postulated, but transitional features in lesions have rarely been demonstrated. We examined human aortic fatty streaks to determine whether significant tendencies toward intimal thickening and toward deep extracellular lipid deposition might be found. To provide accurate ultrastructural assessment of lipid, tissues were processed by new electron microscopic cytochemical techniques....

  14. Transitional features in human atherosclerosis. Intimal thickening, cholesterol clefts, and cell loss in human aortic fatty streaks.

    OpenAIRE

    Guyton, J. R.; Klemp, K. F.

    1993-01-01

    The possible transition from a subset of fatty streaks to fibrous plaques in human atherosclerosis has long been postulated, but transitional features in lesions have rarely been demonstrated. We examined human aortic fatty streaks to determine whether significant tendencies toward intimal thickening and toward deep extracellular lipid deposition might be found. To provide accurate ultrastructural assessment of lipid, tissues were processed by new electron microscopic cytochemical techniques....

  15. Nuclear factor of activated T cells c1 mediates p21-activated kinase 1 activation in the modulation of chemokine-induced human aortic smooth muscle cell F-actin stress fiber formation, migration, and proliferation and injury-induced vascular wall remodeling.

    Science.gov (United States)

    Kundumani-Sridharan, Venkatesh; Singh, Nikhlesh K; Kumar, Sanjay; Gadepalli, Ravisekhar; Rao, Gadiparthi N

    2013-07-26

    Recent literature suggests that cyclin-dependent kinases (CDKs) mediate cell migration. However, the mechanisms were not known. Therefore, the objective of this study is to test whether cyclin/CDKs activate Pak1, an effector of Rac1, whose involvement in the modulation of cell migration and proliferation is well established. Monocyte chemotactic protein 1 (MCP1) induced Pak1 phosphorylation/activation in human aortic smooth muscle cells (HASMCs) in a delayed time-dependent manner. MCP1 also stimulated F-actin stress fiber formation in a delayed manner in HASMCs, as well as the migration and proliferation of these cells. Inhibition of Pak1 suppressed MCP1-induced HASMC F-actin stress fiber formation, migration, and proliferation. MCP1 induced cyclin D1 expression as well as CDK6 and CDK4 activities, and these effects were dependent on activation of NFATc1. Depletion of NFATc1, cyclin D1, CDK6, or CDK4 levels attenuated MCP1-induced Pak1 phosphorylation/activation and resulted in decreased HASMC F-actin stress fiber formation, migration, and proliferation. CDK4, which appeared to be activated downstream of CDK6, formed a complex with Pak1 in response to MCP1. MCP1 also activated Rac1 in a time-dependent manner, and depletion/inhibition of its levels/activation abrogated MCP1-induced NFATc1-cyclin D1-CDK6-CDK4-Pak1 signaling and, thereby, decreased HASMC F-actin stress fiber formation, migration, and proliferation. In addition, smooth muscle-specific deletion of NFATc1 led to decreased cyclin D1 expression and CDK6, CDK4, and Pak1 activities, resulting in reduced neointima formation in response to injury. Thus, these observations reveal that Pak1 is a downstream effector of CDK4 and Rac1-dependent, NFATc1-mediated cyclin D1 expression and CDK6 activity mediate this effect. In addition, smooth muscle-specific deletion of NFATc1 prevented the capacity of vascular smooth muscle cells for MCP-1-induced activation of the cyclin D1-CDK6-CDK4-Pak1 signaling axis, affecting

  16. Insights into acute aortic dissection

    NARCIS (Netherlands)

    Trimarchi, S.

    2012-01-01

    Aortic dissection represents one of the most catastrophic and complex cardiovascular diseases. Its origin is related to an intimal tear with course of blood flow into the aortic wall and division of the aortic lumen into two different lumens, defined as the true and false lumen, separated by a

  17. Muscle Patterning in Mouse and Human Abdominal Wall Development and Omphalocele Specimens of Humans

    OpenAIRE

    Nichol, Peter F.; Corliss, Robert F.; Yamada, Shigehito; SHIOTA, KOHEI; Saijoh, Yukio

    2012-01-01

    Human omphalocele is a congenital defect of the abdominal wall in which the secondary abdominal wall structures (muscle and connective tissue) in an area centered around the umbilicus are replaced by a translucent membranous layer of tissue. Histological examination of omphalocele development and moreover the staging of normal human abdominal wall development has never been described. We hypothesized that omphalocele is the result of an arrest in the secondary abdominal wall development and p...

  18. Determination of oxidation state of iron in normal and pathologically altered human aortic valves

    Energy Technology Data Exchange (ETDEWEB)

    Czapla-Masztafiak, J. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland); Lis, G.J.; Gajda, M.; Jasek, E. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków (Poland); Czubek, U. [Department of Coronary Disease, Jagiellonian University Medical College, John Paul II Hospital, Prądnicka 80, 31-202 Kraków (Poland); Bolechała, F. [Department of Forensic Medicine, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Kraków (Poland); Borca, C. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Kwiatek, W.M. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland)

    2015-12-01

    In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe{sup 3+} is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe{sup 3+} form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

  19. Development of the ventral body wall in the human embryo.

    Science.gov (United States)

    Mekonen, Hayelom K; Hikspoors, Jill P J M; Mommen, Greet; Köhler, S Eleonore; Lamers, Wouter H

    2015-11-01

    Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira reconstruction and cinema 4D remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body.

  20. Role of nitric oxide and inducible nitric oxide synthase in human abdominal aortic aneurysms: a preliminary study

    Institute of Scientific and Technical Information of China (English)

    LIAO Ming-fang; LI Xiao-yan; JING Zai-ping; BAO Jun-min; ZHAO Zhi-qing; MEI Zhi-jun; LU Qing-shen; Feng Xiang; FENG Rui; ZHANG Su-zen

    2006-01-01

    Background Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA.Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszelχ2 test and Kendall' Tau correlation.Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0.05) and the patients with occlusive arteries (P<0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P<0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient=0.5032, P=0.0029)Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.

  1. Aortic insufficiency

    Science.gov (United States)

    ... page, please enable JavaScript. Aortic insufficiency is a heart valve disease in which the aortic valve does not close ... aortic insufficiency Images Aortic insufficiency References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  2. Human uterine wall tension trajectories and the onset of parturition.

    Directory of Open Access Journals (Sweden)

    Peter Sokolowski

    Full Text Available Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000-2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased P < 0.05 compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (P < 0.001, but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension.

  3. Human uterine wall tension trajectories and the onset of parturition.

    Science.gov (United States)

    Sokolowski, Peter; Saison, Francis; Giles, Warwick; McGrath, Shaun; Smith, David; Smith, Julia; Smith, Roger

    2010-06-23

    Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000-2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased P < 0.05 compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (P < 0.001), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension.

  4. 18F-FDG PET-CT uptake is a feature of both normal diameter and aneurysmal aortic wall and is not related to aneurysm size

    Energy Technology Data Exchange (ETDEWEB)

    Barwick, Tara D. [Imperial College Healthcare NHS Trust, Charing Cross Hospital, Department of Radiology/Nuclear Medicine, London (United Kingdom); Hammersmith Hospital, Department of Surgery and Cancer, Imperial College London, London (United Kingdom); Lyons, O.T.A.; Waltham, M. [King' s College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at King' s Health Partners, Academic Department of Surgery, London (United Kingdom); Mikhaeel, N.G. [Guy' s and St Thomas' Foundation NHS Trust, Department of Oncology, London (United Kingdom); O' Doherty, M.J. [King' s Health Partners, Clinical PET Centre, St Thomas' Hospital, London (United Kingdom)

    2014-12-15

    Aortic metabolic activity is suggested to correlate with presence and progression of aneurysmal disease, but has been inadequately studied. This study investigates the 2-[{sup 18}F] fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) uptake in a population of infra-renal abdominal aortic aneurysms (AAA), compared to a matched non-aneurysmal control group. The Positron Emission Tomography - Computed Tomography (PET/CT) database was searched for infra-renal AAA. Exclusion criteria were prior repair, vasculitis, and saccular/mycotic thoracic or thoraco-abdominal aneurysms. Matching of 159 non-aneurysmal (<3 cm diameter) controls from the same population was assessed. Infra-renal aortic wall FDG uptake was assessed using visual analysis; maximum standardized uptake value (SUV{sub max}) and target to background mediastinal blood pool ratio (TBR) were documented. Predictors of FDG uptake (age, sex, aortic diameter, hypertension, statin use, and diabetes) were assessed using univariate analysis. Follow-up questionnaires were sent to referring clinicians. Aneurysms (n = 151) and controls (n = 159) were matched (p > 0.05) for age, sex, diabetes, hypertension, smoking status, statin use, and indication for PET/CT. Median aneurysm diameter was 5.0 cm (range 3.2-10.4). On visual analysis there was no significant difference in the overall numbers with increased visual uptake 24 % (36/151) in the aneurysm group vs. 19 % (30/159) in the controls, p = ns. SUV{sub max} was slightly lower in the aneurysm group vs. controls (mean (2 SD) 1.75(0.79) vs. 1.84(0.58), p = 0.02). However there was no difference in TBR between the AAA group and controls (mean (2 SD) 1.03 (0.46) vs. 1.05(0.31), p = 0.36). During a median 18 (interquartile range 8-35) months' follow-up 20 were repaired and four were confirmed ruptured. The level of metabolic activity as assessed by {sup 18}F-FDG PET/CT in infra-renal AAA does not correlate with aortic size and does not differ between aneurysms and matched controls

  5. Abdominal wall repair with human acellular dermal autograft

    Directory of Open Access Journals (Sweden)

    Roel E. Genders

    2011-12-01

    Full Text Available Repair of abdominal wall defects in the presence of contamination or infection is a significant problem. The loss of tissue warrants enforcement of the abdominal wall, preferably by autologous material. However, autologous repair often requires extensive surgery. This paper presents a review of available literature of placement of an acellular human dermis to repair an abdominal fascia defect, in contaminated as well as in non-contaminated surgical fields. It is illustrated with a case report that describes the successful reconstruction of an infected abdominal wall defect with a human acellular dermis allograft. A systematic literature review was undertaken with searches performed in the Pubmed and Cochrane databases for the period up till March 2009, using the search terms Alloderm [Substance Name], Hernia [Mesh] and the key words acellular dermis, acellular dermal matrix, human acellular dermal allograft and abdominal wall defect. To assess methodological quality, each article was subjected to a modification of the methodological index for non-randomized studies (MINORS according to Slim et al. Two items from the original index were not included because none of the studies selected had an unbiased assessment of the study end points and in none of the studies was a prospective calculation of the study size performed. Seventeen studies were included in the review. Data were extracted regarding study design, number of patients, surgical technique, followup period, contaminated or non-contaminated area of the fascia defect, mortality and morbidity (hemorrhage, seroma, wound dehiscence, infection of the operative procedure, the longterm results (removal of the graft, reherniation and bulging and level of evidencey. A total of 169 short-term complications and 151 longterm complications occurred after 643 surgical procedures reconstructing both contaminated and clean abdominal wall defects by implantation of an HADA. Human acellular dermal allograft

  6. Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

    Science.gov (United States)

    Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

    2000-01-01

    This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (Pmuscle cells is likely due to transient membrane disruption on initiation of flow.

  7. Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm.

    Science.gov (United States)

    Camacho, Mercedes; Dilmé, Jaume; Solà-Villà, David; Rodríguez, Cristina; Bellmunt, Sergi; Siguero, Laura; Alcolea, Sonia; Romero, José-María; Escudero, José-Román; Martínez-González, José; Vila, Luis

    2013-12-01

    We investigated the prostaglandin (PG)E2 pathway in human abdominal aortic aneurysm (AAA) and its relationship with hypervascularization. We analyzed samples from patients undergoing AAA repair in comparison with those from healthy multiorgan donors. Patients were stratified according to maximum aortic diameter: low diameter (LD) (PGE2 metabolites were higher in AAA than in controls (plasma-controls, 19.9 ± 2.2; plasma-AAA, 38.8 ± 5.5 pg/ml; secretion-normal aorta, 16.5 ± 6.4; secretion-AAA, 72.9 ± 6.4 pg/mg; mean ± SEM). E-prostanoid receptor (EP)-2 and EP-4 were overexpressed in AAA, EP-4 being the only EP substantially expressed and colocalized with mPGES-1 in the microvasculature. Additionally, EP-4 mediated PGE2-induced angiogenesis in vitro. We provide new data concerning mPGES-1 expression in human AAA. Our findings suggest the potential relevance of the COX-2/mPGES-1/EP-4 axis in the AAA-associated hypervascularization.

  8. Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

    Science.gov (United States)

    Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

    2000-01-01

    This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (Pmuscle cells is likely due to transient membrane disruption on initiation of flow.

  9. Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells

    Directory of Open Access Journals (Sweden)

    Zhimin Fu

    2016-01-01

    Full Text Available We aimed to explore the effects of raloxifene (RAL on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs. Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group. Meanwhile, the results of flow cytometry of the cells collected after seven days showed that the ratio of the S stage and the cell apoptosis rate of AVICs can be significantly reduced by RAL in the concentration groups of 10 and 100 nmol/L. The mRNA and protein expressions of caspase-3 and caspase-8 were significantly decreased compared with those in the control group. This study laid the foundation for further treatment of aortic valve disease by using RAL.

  10. Impact of intra-aortic balloon counterpulsation with different balloon volumes on cardiac performance in humans.

    Science.gov (United States)

    Cohen, Marc; Fasseas, Panayotis; Singh, Varinder P; McBride, Ruth; Orford, James L; Kussmaul, William G

    2002-10-01

    Intra-aortic balloon (IAB) counterpulsation can augment the cardiac output. However, the effect of different IAB volumes on cardiac performance has not been adequately evaluated in humans. Eighty-two patients (52 males [63%]; mean age, 65 +/- 12 years; mean body surface area [BSA], 1.8 +/- 0.2 m(2)) had IAB counterpulsation for cardiogenic shock, refractory angina, and preoperatively for high-risk cardiac surgery. Cardiac hemodynamics were prospectively studied during IAB with inflation volumes of 32 vs. 40 cc. Hemodynamic data collected included aortic pressure, pulmonary artery pressure, systemic and mixed venous oxygen saturations, and cardiac output (by Fick). Transthoracic echocardiography (TTE) was used to obtain both velocity time integrals (VTIs) and the area of the left ventricular outflow tract (LVOT). Left ventricular stroke volume was then calculated as LVOT area x VTI. Cardiac output (CO) determined by the Fick method and VTI did not differ significantly (P = NS) between the two inflation volumes (y = 0.002 + 0.97x). In a subgroup of 33 patients with BSA

  11. Molecular-level characterization of elastin-like constructs and human aortic elastin.

    Science.gov (United States)

    Heinz, Andrea; Schräder, Christoph U; Baud, Stéphanie; Keeley, Fred W; Mithieux, Suzanne M; Weiss, Anthony S; Neubert, Reinhard H H; Schmelzer, Christian E H

    2014-09-01

    This study aimed to characterize the structures of two elastin-like constructs, one composed of a cross-linked elastin-like polypeptide and the other one of cross-linked tropoelastin, and native aortic elastin. The structures of the insoluble materials and human aortic elastin were investigated using scanning electron microscopy. Additionally, all samples were digested with enzymes of different specificities, and the resultant peptide mixtures were characterized by ESI mass spectrometry and MALDI mass spectrometry. The MS(2) data was used to sequence linear peptides, and cross-linked species were analyzed with the recently developed software PolyLinX. This enabled the identification of two intramolecularly cross-linked peptides containing allysine aldols in the two constructs. The presence of the tetrafunctional cross-link desmosine was shown for all analyzed materials and its quantification revealed that the cross-linking degree of the two in vitro cross-linked materials was significantly lower than that of native elastin. Molecular dynamics simulations were performed, based on molecular species identified in the samples, to follow the formation of elastin cross-links. The results provide evidence for the significance of the GVGTP hinge region of domain 23 for the formation of elastin cross-links. Overall, this work provides important insight into structural similarities and differences between elastin-like constructs and native elastin. Furthermore, it represents a step toward the elucidation of the complex cross-linking pattern of mature elastin. Copyright © 2014. Published by Elsevier B.V.

  12. A custom image-based analysis tool for quantifying elastin and collagen micro-architecture in the wall of the human aorta from multi-photon microscopy.

    Science.gov (United States)

    Koch, Ryan G; Tsamis, Alkiviadis; D'Amore, Antonio; Wagner, William R; Watkins, Simon C; Gleason, Thomas G; Vorp, David A

    2014-03-21

    The aorta possesses a micro-architecture that imparts and supports a high degree of compliance and mechanical strength. Alteration of the quantity and/or arrangement of the main load-bearing components of this micro-architecture--the elastin and collagen fibers--leads to mechanical, and hence functional, changes associated with aortic disease and aging. Therefore, in the future, the ability to rigorously characterize the wall fiber micro-architecture could provide insight into the complicated mechanisms of aortic wall remodeling in aging and disease. Elastin and collagen fibers can be observed using state-of-the-art multi-photon microscopy. Image-analysis algorithms have been effective at characterizing fibrous constructs using various microscopy modalities. The objective of this study was to develop a custom MATLAB-language automated image-based analysis tool to describe multiple parameters of elastin and collagen micro-architecture in human soft fibrous tissue samples using multi-photon microscopy images. Human aortic tissue samples were used to develop the code. The tool smooths, cleans and equalizes fiber intensities in the image before segmenting the fibers into a binary image. The binary image is cleaned and thinned to a fiber skeleton representation of the image. The developed software analyzes the fiber skeleton to obtain intersections, fiber orientation, concentration, porosity, diameter distribution, segment length and tortuosity. In the future, the developed custom image-based analysis tool can be used to describe the micro-architecture of aortic wall samples in a variety of conditions. While this work targeted the aorta, the software has the potential to describe the architecture of other fibrous materials, tube-like networks and connective tissues.

  13. Effect of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    刘曜蓉

    2013-01-01

    Objective To investigate the impact of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells (HASMCs) .Methods Uremic serum was incubated at 37℃for 3days.Calcium phosphate crystals and uremic supernatant were isolated from uremic serum by ultracentrifugation.

  14. High Central Aortic Rather than Brachial Blood Pressure is Associated with Carotid Wall Remodeling and Increased Arterial Stiffness in Childhood.

    Science.gov (United States)

    Peluso, Gonzalo; García-Espinosa, Victoria; Curcio, Santiago; Marota, Marco; Castro, Juan; Chiesa, Pedro; Giachetto, Gustavo; Bia, Daniel; Zócalo, Yanina

    2017-03-01

    In adults, central blood pressure (cBP) is reported to associate target organ damages (TODs) rather than peripheral blood pressure (pBP). However, data regarding the association of pre-clinical TODs with cBP and pBP in pediatric populations are scarce. To evaluate in children and adolescents the importance of cBP and pBP levels, in terms of their association with hemodynamic and vascular changes. 315 subjects [age (mean/range) 12/8-18 years] were included. pBP (oscillometry, Omron-HEM433INT and Mobil-O-Graph), cBP levels and waveforms (oscillometry, Mobil-O-Graph; applanation tonometry, SphygmoCor), aortic wave reflection-related parameters, carotid intima-media thickness (CIMT) and carotid (elastic modulus, stiffness-index) and aortic stiffness (carotid-femoral pulse wave velocity, PWV). Four groups were defined considering pBP and cBP percentiles (th): cBP ≥90th, cBP blood pressure (cBP or pBP). Subgroups were matched for anthropometric and cardiovascular risk factors (propensity matching-score). Subjects with high cBP showed a worse cardiovascular risk profile in addition to worse peripheral hemodynamic conditions. The CIMT, carotid and aortic stiffness levels were also higher in those subjects. CIMT and carotid stiffness remained statistically higher when subjects were matched for pBP and other cardiovascular risk factors. There were no differences in arterial properties when subjects were analyzed (compared) considering similar pBP levels, during normal and high cBP conditions. Compared with pBP, the cBP levels show a greater association with vascular alterations (high CIMT and arterial stiffness), in children and adolescents.

  15. Muscle patterning in mouse and human abdominal wall development and omphalocele specimens of humans.

    Science.gov (United States)

    Nichol, Peter F; Corliss, Robert F; Yamada, Shigehito; Shiota, Kohei; Saijoh, Yukio

    2012-12-01

    Human omphalocele is a congenital defect of the abdominal wall in which the secondary abdominal wall structures (muscle and connective tissue) in an area centered around the umbilicus are replaced by a translucent membranous layer of tissue. Histological examination of omphalocele development and moreover the staging of normal human abdominal wall development has never been described. We hypothesized that omphalocele is the result of an arrest in the secondary abdominal wall development and predicted that we would observe delays in myoblast maturation and an arrest in secondary abdominal wall development. To look for evidence in support of our hypothesis, we performed a histological analysis of normal human abdominal wall development and compared this to mouse. We also conducted the first histological analysis of two human specimens with omphalocele. In these two omphalocele specimens, secondary abdominal wall development appears to have undergone an arrest around Carnegie Stage 19. In both specimens disruptions in the unidirectional orientation of myofibers were observed in the external and internal obliques, and rectus abdominis but not in the transversus abdominis. These latter findings support a model of normal abdominal wall development in which positional information instructs the orientation of myoblasts as they organize into individual muscle groups.

  16. Rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells

    Institute of Scientific and Technical Information of China (English)

    YANG Shui-xiang 杨水祥; YAN Juan 闫娟; Shailesh S. Deshpande; Kaikobad Irani; Charles J. Lowenstein

    2004-01-01

    Background The release of Weibel-Palade Bodies (WPB) is a form of endothelial cell activation. But the signal transduction pathway leading to WPB release is not yet defined. We hypothesized that small G-protein rac1 and reactive oxygen species (ROS) mediate the ligand induced release of Weibel-Palade Bodies. Methods We tested this hypothesis by using wild-type and mutant adenoviral rac1 expression vectors, and by manipulating the production and destruction of superoxide and hydrogen peroxide in human aortic endothelial cells (HAEC). Results Thrombin (1.0 Unit, 30 min) induced the increase of WPB release by 3.7-fold in HAEC, and that H2O2 (0.1 mmol/L, 30 min) induced by 4.5-fold. These results correlated with thrombin-stimulated activation of rac-GTP binding activity by 3.5-fold, and increase of ROS production by 3.4-fold. The dominant negative adenoviral rac-N17 gene transfer dramatically inhibited the release of WPB by 64.2% (control) and 77.3% (thrombin-stimulation), and decreased ROS production by 65.5% (control) and 83.6% (thrombin-stimulation) compared with non-infected cells, respectively. Anti-oxidants, catalase and N-acetyl-cysteine significantly decreased the release of WPB by 34% and 79% in control cells, and further decreased by 63.6% and 46.7% in rac-N17 transferred cells compared with non-infected cells. We also confirmed that rac1 was located upstream of ROS in the WPB release pathway. Conclusions Small G-protein rac1 medicates ligand-induced release of Weibel-Palade Bodies in human aortic endothelial cells, and the signal pathway of WPB release is a rac1-dependent ROS regulating mechanism.

  17. Measurements of ultrasonic pulse distortion produced by human chest wall.

    Science.gov (United States)

    Hinkelman, L M; Szabo, T L; Waag, R C

    1997-04-01

    Ultrasonic wavefront distortion produced by transmission through human chest wall specimens was measured over a two-dimensional aperture. Measured pulse wavefronts were sometimes disrupted by secondary wavefronts produced by interaction between the transmitted pulses and the bone and cartilage structures of the rib cage. The secondary wavefronts produced large distortions in the received waveforms and interfered with the determination of the wavefront distortion caused by soft-tissue inhomogeneities. The effects of secondary wavefronts were minimized by reducing the region of analysis. Differences in arrival time and energy level between these restricted regions and references that account for geometric delay and spreading were computed. Spectral changes were assessed by calculating a waveform similarity factor that is decreased from 1.0 by changes in waveform shape. For 16 different intercostal spaces, the arrival time fluctuations of the measured waveforms had an average (+/-s.d.) rms value of 21.3 (+/-8.4) ns and an average correlation length of 2.50 (+/-0.62) mm. The energy level fluctuations had an average rms value of 1.57 (+/-0.45) dB and an average correlation length of 1.98 (+/-0.33) mm, and the average waveform similarity factor was 0.964 (+/-0.012). For soft-tissue inhomogeneities in chest wall specimens, the average rms arrival time and energy level fluctuations were less than half those measured for the abdominal wall. However, although the average correlation length of the arrival time fluctuations was less than half that found for the abdominal wall, the average correlation length of the energy level fluctuations was similar to that of the abdominal wall.

  18. Post-stenotic aortic dilatation

    Directory of Open Access Journals (Sweden)

    Jahangiri Marjan

    2006-03-01

    Full Text Available Abstract Aortic stenosis is the most common valvular heart disease affecting up to 4% of the elderly population. It can be associated with dilatation of the ascending aorta and subsequent dissection. Post-stenotic dilatation is seen in patients with AS and/or aortic regurgitation, patients with a haemodynamically normal bicuspid aortic valve and following aortic valve replacement. Controversy exists as to whether to replace the aortic root and ascending aorta at the time of aortic valve replacement, an operation that potentially carries a higher morbidity and mortality. The aetiology of post-stenotic aortic dilatation remains controversial. It may be due to haemodynamic factors caused by a stenotic valve, involving high velocity and turbulent flow downstream of the stenosis, or due to intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling in the aortic wall including inadequate synthesis, degradation and transport of extracellular matrix proteins. This article reviews the aetiology, pathology and management of patients with post-stenotic aortic dilatation.

  19. Subcoronary versus supracoronary aortic stenosis. an experimental evaluation

    Directory of Open Access Journals (Sweden)

    Hasenkam J Michael

    2011-08-01

    Full Text Available Abstract Background Valvular aortic stenosis is the most common cause of left ventricular hypertrophy due to gradually increasing pressure work. As the stenosis develop the left ventricular hypertrophy may lead to congestive heart failure, increased risk of perioperative complications and also increased risk of sudden death. A functional porcine model imitating the pathophysiological nature of valvular aortic stenosis is very much sought after in order to study the geometrical and pathophysiological changes of the left ventricle, timing of surgery and also pharmacological therapy in this patient group. Earlier we developed a porcine model for aortic stenosis based on supracoronary aortic banding, this model may not completely imitate the pathophysiological changes that occurs when valvular aortic stenosis is present including the coronary blood flow. It would therefore be desirable to optimize this model according to the localization of the stenosis. Methods In 20 kg pigs subcoronary (n = 8, supracoronary aortic banding (n = 8 or sham operation (n = 4 was preformed via a left lateral thoracotomy. The primary endpoint was left ventricular wall thickness; secondary endpoints were heart/body weight ratio and the systolic/diastolic blood flow ratio in the left anterior descending coronary. Statistical evaluation by oneway anova and unpaired t-test. Results Sub- and supracoronary banding induce an equal degree of left ventricular hypertrophy compared with the control group. The coronary blood flow ratio was slightly but not significantly higher in the supracoronary group (ratio = 0.45 compared with the two other groups (subcoronary ratio = 0.36, control ratio = 0.34. Conclusions A human pathophysiologically compatible porcine model for valvular aortic stenosis was developed by performing subcoronary aortic banding. Sub- and supracoronary aortic banding induce an equal degree of left ventricular hypertrophy. This model may be valid for experimental

  20. Monocyte migration into the subendothelial space of a coculture of adult human aortic endothelial and smooth muscle cells.

    OpenAIRE

    Navab, M; Hough, G P; Stevenson, L W; Drinkwater, D C; Laks, H; Fogelman, A M

    1988-01-01

    Human aortic endothelial cells (EC) and smooth muscle cells (SMC) were isolated and used to form a multilayer of EC-SMC separated by a layer of collagen. SMC and/or collagen layers exerted minimal effects on Na+ transport but impeded the transport of LDL. The presence of an endothelial monolayer markedly reduced the transport of Na+ and LDL. When monocytes were presented to the complete coculture, in the absence of added chemoattractant, one monocyte entered the subendothelial space for every...

  1. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells

    OpenAIRE

    Valentina Spigoni; Pedro Mena; Monia Cito; Federica Fantuzzi; Bonadonna, Riccardo C.; Furio Brighenti; Alessandra Dei Cas; Daniele Del Rio

    2016-01-01

    The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithi...

  2. CT of thoracic aortic aneurysms.

    Science.gov (United States)

    Posniak, H V; Olson, M C; Demos, T C; Benjoya, R A; Marsan, R E

    1990-09-01

    Aneurysms of the thoracic aorta are most often the result of arteriosclerotic disease. Other causes include degeneration of the medial layer of the aortic wall, either idiopathically or due to genetic disorders such as Marfan syndrome; aortic dissection; trauma; syphilis and other bacterial infection; noninfective aortitis; and congenital anomaly. We review normal anatomy of the aorta and discuss our technique and interpretation of computed tomography (CT) in the evaluation of the thoracic aorta. We illustrate the CT appearance of different types of aortic aneurysms as well as discuss the use of CT for assessing complications of aneurysms, for postoperative follow-up, and in the differentiation of aortic aneurysm from a paraaortic mass.

  3. Plasma levels of cathepsins L, K, and V and risks of abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lv, Bing-Jie; Lindholt, Jes S; Wang, Jing;

    2013-01-01

    Cathepsin L (CatL), cathepsin K (CatK), and cathepsin V (CatV) are potent elastases implicated in human arterial wall remodeling. Whether plasma levels of these cathepsins are altered in patients with abdominal aortic aneurysms (AAAs) remains unknown.......Cathepsin L (CatL), cathepsin K (CatK), and cathepsin V (CatV) are potent elastases implicated in human arterial wall remodeling. Whether plasma levels of these cathepsins are altered in patients with abdominal aortic aneurysms (AAAs) remains unknown....

  4. Passive cigarette smoking induces inflammatory injury in human arterial walls

    Institute of Scientific and Technical Information of China (English)

    ZOU Ni; HONG Jiang; DAI Qiu-yan

    2009-01-01

    Background Epidemiological studies have shown that both active and passive cigarette smoking increase the risk of atherosclerosis. But very little is known about the biological processes induced by passive cigarette smoking that contribute to atheresclerosis. We observe the expression of a few of biological and inflammatory markers in human arterial walls in vitro which were treated with the second-hand smoke solution (sidestream whole, SSW), and discuss the possible mechanism of inflammatory injury induced by second-hand smoke.Methods The biological markers (platelet endothelial cell adhesion molecule-1, PECAM-1; α-smooth muscle actin, α-SMA; collagen Ⅳ, Col Ⅳ) and inflammatory markers (vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1; interleukin-8, IL-8) of human aortal wall were tested by immunofluorescence staining. The levels of MCP-1 and IL-8 mRNA expression were detected by reverse transcription-polymerase chain reaction (RT-PCR).Results No distinct difference was observed between SSW and the control group on the expression of biological markers as assessed by the light microscope. But the inflammatory markers VCAM-1, MCP-1 and IL-8 on the subendothelial layer and smooth muscle cell layers, which are near the endothelium of arterial wall, were strongly stained in the SSW group compared with the control group. Their fluorescence intensities in the 1:40 SSW group (VCAM-1: 0.35±0.04, MCP-1: 0.34±0.05, IL-8: 0.37±0.05) and the 1:20 SSW group (VCAM-1: 0.40±0.04, MCP-1: 0.52±0.09, IL-8: 0.51±0.07) were significantly stronger than the control group (VCAM-1: 0.12±0.04, MCP-1: 0.06±0.02, IL-8: 0.24±0.03) by semi-quantitative analysis of immunofluorescence (P <0.001 vs control). MCP-1 mRNA expression in the 1:40 SSW (0.15±0.04) and the 1:20 SSW (0.19±0.06) group was significantly higher than in the control group (0.09±0.03) (P <0.05, P <0.01 vs control); IL-8 mRNA expression in the 1:40 SSW (0.64±0.12) and 1

  5. Soluble TWEAK plasma levels predict expansion of human abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Martín-Ventura, J L; Lindholt, Jes S.; Pavón Moreno, Miguel Ángel;

    2010-01-01

    Diminished soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) concentrations are associated with cardiovascular diseases. We have analyzed sTWEAK levels and its relation with expansion rate in subjects with abdominal aortic aneurysm (AAA)....

  6. Increased apoptosis and decreased density of medial smooth muscle cells in human abdominal aortic aneurysms

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian张健; Jan Schmidt; Eduard Ryschich; Hardy Schumacher; Jens R Allenberg

    2003-01-01

    Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P<0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF, P<0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA, which may profoundly influence the development of AAA.

  7. MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xiumei Xie

    2012-03-01

    Full Text Available Muramyldipeptide (MDP, the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2. Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.

  8. MDP up-regulates the gene expression of type I interferons in human aortic endothelial cells.

    Science.gov (United States)

    Lv, Qingshan; Yang, Mei; Liu, Xueting; Zhou, Lina; Xiao, Zhilin; Chen, Xiaobin; Chen, Meifang; Xie, Xiumei; Hu, Jinyue

    2012-03-23

    Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs) with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF) 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.

  9. In Vitro Effects of Hollow Gold Nanoshells on Human Aortic Endothelial Cells

    Science.gov (United States)

    Gu, Chunrong; Wu, Hengfang; Ge, Gaoyuan; Li, Xiongzhi; Guo, Zhirui; Bian, Zhiping; Xu, Jindan; Lu, Hua; Chen, Xiangjian; Yang, Di

    2016-09-01

    Gold nanoparticles are emerging as promising biomedical tools due to their unique nanoscale characteristics. Our purpose was to synthesize a hollow-shaped gold nanoparticle and to investigate its effect on human aortic endothelial cells (HAECs) in vitro. Hollow gold nanoshells with average 35-nm diameters and 10-nm shell thickness were obtained by galvanic replacement using quasi-spherical nanosilver as sacrifice-template. Our results showed that hollow gold nanoshells in the culture medium could be internalized into the cytoplasm of HAECs. No cytotoxicity effect of hollow gold nanoshells on HAECs was observed within the test concentrations (0-0.8 μg/mL) and test exposure period (0-72 h) by tetrazolium dye assay. Meanwhile, the release of cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without hollow gold nanoshells). The concentrations of vasodilators, nitric oxide, and prostacyclin I-2 were not changed, but the vasoconstrictor endothelin-1 was decreased by hollow gold nanoshells treatment in HAECs. HAECs exposed to hollow gold nanoshells resulted in suppressing expressions of genes involved in apoptosis and activating expressions of genes of adhesion molecules. Moreover, we demonstrated by in vitro endothelial tube formation that hollow gold nanoshells (0.8 μg/mL) could not inhibit angiogenesis by the HAECs. Altogether, these results indicate that the structure and major function of HAECs would not be disrupted by hollow gold nanoshell treatment.

  10. Effects of macro- versus nanoporous silicon substrates on human aortic endothelial cell behavior

    Science.gov (United States)

    Formentín, Pilar; Alba, María; Catalán, Úrsula; Fernández-Castillejo, Sara; Pallarès, Josep; Solà, Rosà; Marsal, Lluís F.

    2014-08-01

    Human aortic endothelial cells play a key role in the pathogenesis of atherosclerosis, which is a common, progressive, and multifactorial disease that is the clinical endpoint of an inflammatory process and endothelial dysfunction. Study and development of new therapies against cardiovascular disease must be tested in vitro cell models, prior to be evaluated in vivo . To this aim, new cell culture platforms are developed that allow cells to grow and respond to their environment in a realistic manner. In this work, the cell adhesion and morphology of endothelial cells are investigated on functionalized porous silicon substrates with two different pore size configurations: macroporous and nanoporous silicon. Herein, we modified the surfaces of porous silicon substrates by aminopropyl triethoxysilane, and we studied how different pore geometries induced different cellular response in the cell morphology and adhesion. The cell growth over the surface of porous silicon becomes an attractive field, especially for medical applications. Surface properties of the biomaterial are associated with cell adhesion and as well as, with proliferation, migration and differentiation.

  11. Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells.

    Science.gov (United States)

    Fong, Lai Yen; Ng, Chin Theng; Zakaria, Zainul Amiruddin; Baharuldin, Mohamad Taufik Hidayat; Arifah, Abdul Kadir; Hakim, Muhammad Nazrul; Zuraini, Ahmad

    2015-10-01

    The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC). TNF-α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-α-induced increased permeability. Asiaticoside also prevented TNF-α-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization.

  12. Calcium Phosphate Crystals from Uremic Serum Promote Osteogenic Differentiation in Human Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Liu, Yaorong; Zhang, Lin; Ni, Zhaohui; Qian, Jiaqi; Fang, Wei

    2016-11-01

    Recent study demonstrated that calcium phosphate (CaP) crystals isolated from high phosphate medium were a key contributor to arterial calcification. The present study further investigated the effects of CaP crystals induced by uremic serum on calcification of human aortic smooth muscle cells. This may provide a new insight for the development of uremic cardiovascular calcification. We tested the effects of uremic serum or normal serum on cell calcification. Calcification was visualized by staining and calcium deposition quantified. Expression of various bone-calcifying genes was detected by real-time PCR, and protein levels were quantified by western blotting or enzyme-linked immunosorbent assays. Pyrophosphate was used to investigate the effects of CaP crystals' inhibition. Finally, CaP crystals were separated from uremic serum to determine its specific pro-calcification effects. Uremic serum incubation resulted in progressively increased calcification staining and increased calcium deposition in HASMCs after 4, 8 and 12 days (P vs 0 day crystals with pyrophosphate incubation prevented calcium deposition and bone-calcifying gene over-expression increased by uremic serum. CaP crystals, rather than the rest of uremic serum, were responsible for these effects. Uremic serum accelerates arterial calcification by mediating osteogenic differentiation. This effect might be mainly attributed to the CaP crystal content.

  13. Human aortic endothelial cell response to 316L stainless steel material microstructure.

    Science.gov (United States)

    Choubey, Animesh; Marton, Denes; Sprague, Eugene A

    2009-10-01

    The role of metal microstructure (e.g. grain sizes) in modulating cell adherence behavior is not well understood. This study investigates the effect of varying grain sizes of 316L stainless steel (SS) on the attachment and spreading of human aortic endothelial cells (HAECs). Four different grain size samples; from 16 to 66 microm (ASTM 9.0-4.9) were sectioned from sheets. Grain structure was revealed by polishing and etching with glycergia. Contact angle measurement was done to assess the hydrophilicity of the specimens. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) were used to characterize the roughness and surface chemistry of the specimens. Cells were seeded on mechanically polished and chemically etched specimens followed by identification of activated focal adhesion sites using fluorescently tagged anti-pFAK (phosphorylated focal adhesion kinase). The 16 microm grain size etched specimens had significantly (P < 0.01) higher number of cells attached per cm(2) than other specimens, which may be attributed to the greater grain boundary area and associated higher surface free energy. This study shows that the underlying material microstructure may influence the HAEC behavior and may have important implications in endothelialization.

  14. Influence of nanoporous poly(ether imide) particle extracts on human aortic endothelial cells (HAECs).

    Science.gov (United States)

    Kumar, Reddi K; Basu, Sayantani; Lemke, Horst-Dieter; Jankowski, Joachim; Kratz, Karl; Lendlein, Andreas; Tetali, Sarada D

    2016-01-01

    Accumulated uremic toxins like indoxyl sulphate, hippuric acid and p-cresyl sulphates in renal failure patients stimulate proinflammatory effects, and consequently kidney and cardiovascular diseases. Low clearance rate of these uremic toxins from the blood of uremic patients by conventional techniques like hemodialysis is due to their strong covalent albumin binding (greater than 95%) and hydrophobic nature, which led to alternatives like usage of hydrophobic adsorber's in removing these toxins from the plasma of kidney patients. Polymers like polyethylene, polyurethane, polymethylmethacrylate, cellophane and polytetrafluoroethylene were already in use as substitutes for metal devices as dialysis membranes. Among new synthetic polymers, one such ideal adsorber material are highly porous microparticles of poly(ether imide) (PEI) with diameters in the range from 50-180μm and a porosity around 88±2% prepared by a spraying and coagulation process.It is essential to make sure that these synthetic polymers should not evoke any inflammatory or apoptotic response during dialysis. Therefore in our study we evaluated in vitro effect of PEI microparticle extracts in human aortic endothelial cells (HEACs) concerning toxicity, inflammation and apoptosis. No cell toxicity was observed when HAECs were treated with PEI extracts and inflammatory/apoptotic markers were not upregulated in presence of PEI extracts. Our results ensure biocompatibility of PEI particles and further hemocompatibility of particles will be tested.

  15. Co-cultivation of human aortic smooth muscle cells with epicardial adipocytes affects their proliferation rate.

    Science.gov (United States)

    Ždychová, J; Čejková, S; Králová Lesná, I; Králová, A; Malušková, J; Janoušek, L; Kazdová, L

    2014-01-01

    The abnormal proliferation of vascular smooth muscle cells (VSMC) is thought to play a role in the pathogenesis of atherosclerosis. Adipocytes produce several bioactive paracrine substances that can affect the growth and migration of VSMCs. Our study focuses on the direct effect of the bioactive substances in conditioned media (CM) that was obtained by incubation with primary adipocyte-derived cell lines, including cell lines derived from both preadipocytes and from more mature cells, on the proliferation rate of human aortic smooth muscle cells (HAoSMCs). We used a Luminex assay to measure the adipokine content of the CM and showed that there was a higher concentration of monocyte chemoattractant protein-1 in renal preadipocyte-CM compared with the HAoSMC control (p<0.5). The addition of both renal preadipocyte- and epicardial adipocyte- CM resulted in the elevated production of vascular endothelial growth factor compared with the control HASoSMC CM (p<0.001). The adiponectin content in renal adipocyte-CM was increased compared to all the remaining adipocyte-CM (p<0.01). Moreover, the results showed a higher proliferation rate of HAoSMCs after co-culture with epicardial adipocyte-CM compared to the HAoSMC control (p<0.05). These results suggest that bioactive substances produced by adipocytes have a stimulatory effect on the proliferation of VSMCs.

  16. Effect of age on aortic atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Michael A. Chen; Miwa Kawakubo; Patrick M. Colletti; Dongxiang Xu; Laurie LaBree Dustin; Robert Detrano; Stanley P Azen; Nathan D. Wong; Xue-Qiao Zhao

    2013-01-01

    Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). Methods A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated. Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI × 100. Results In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area and wall thickness were 222 ± 45 mm2 and 2.7 ± 0.4 mm, respectively. Maximum wall thickness was 3.4 ± 0.6 mm, and PWV was 32% ± 4%. Women appeared to have smaller wall area, but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associated with larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors, Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcification was associated with coronary calcification. Conclusions Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, and women had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.

  17. [Inflammatory abdominal aortic aneurysm].

    Science.gov (United States)

    Ziaja, K; Sedlak, L; Urbanek, T; Kostyra, J; Ludyga, T

    2000-01-01

    The reported incidence of inflammatory abdominal aortic aneurysm (IAAA) is from 2% to 14% of patients with abdominal aortic aneurysm and the etiology of this disease is still discussed--according to the literature several pathogenic theories have been proposed. From 1992 to 1997 32 patients with IAAA were operated on. The patients were mostly symptomatic--abdominal pain was present in 68.75% cases, back pain in 31.25%, fever in 12.5% and weight loss in 6.25% of the operated patients. In all the patients ultrasound examination was performed, in 4 patients CT and in 3 cases urography. All the patients were operated on and characteristic signs of inflammatory abdominal aortic aneurysm like: thickened aortic wall, perianeurysmal infiltration or retroperitoneal fibrosis with involvement of retroperitoneal structures were found. In all cases surgery was performed using transperitoneal approach; in three cases intraoperatively contiguous abdominal organs were injured, which was connected with their involvement into periaortic inflammation. In 4 cases clamping of the aorta was done at the level of the diaphragmatic hiatus. 3 patients (9.37%) died (one patient with ruptured abdominal aortic aneurysm). Authors present diagnostic procedures and the differences in the surgical tactic, emphasizing the necessity of the surgical therapy in patients with inflammatory abdominal aortic aneurysm.

  18. The interaction between human low density lipoproteins and bovine aortic endothelial cells. Measurements of membrane fluidity.

    Science.gov (United States)

    Badea, M G; Sima, A; Jinga, V V; Hörer, O

    1989-01-01

    Bovine aortic endothelial cells in culture have been incubated with human low density lipoproteins (LDL) characterized in their cholesterol content. The incubation was done at different time intervals up to 72 h and various LDL concentrations. It began after endothelial cells had been starved for 24 h in lipoprotein deficient serum. The transfer of some LDL-components to endothelial cells plasmalemma was monitored by measurements of membrane fluidity. Namely, the fluorescent probe trimethylamonio-diphenyl hexatriene was inserted in the cell membrane and fluorescence anisotropy was determined; a higher fluorescence anisotropy means a higher rigidity of the plasmalemma. The results show that the rigidity of the endothelial cell plasmalemma increased progressively with the time of incubation (+11% to +19.5% after 24 h and 72 h, respectively for the concentration of 200 micrograms. LDL-cholesterol/dish) and with the greater amount of cholesterol in LDL (+10.9%) for 200 micrograms LDL-cholesterol/dish to +15% for 800 micrograms LDL-cholesterol/dish after 24 h incubation). In order to see if the LDL material transfer proceeded by receptor-mediated endocytosis of LDL and/or directly through aqueous solution a lysosomal inhibitor, chloroquine, was used at the concentration of 20 microM for preventing the lysosomal hydrolase activity. In the presence of this inhibitor the fluorescence anisotropy in treated endothelial cells increased by a lesser amount, suggesting an approx. 30% participation of intracellular route. Therefore, the transfer of material (probably cholesterol) from LDL to endothelial plasmalemma could take place both by receptor-mediated endocytosis and directly through the aqueous solution.

  19. [Dehiscence of the Pericardial Patch, after Surgical Treatment of Active Infective Aortic Valve Endocarditis with Reconstruction of the Aortic Annulus Using a Glutaraldehyde-treated Autologous Pericardium].

    Science.gov (United States)

    Yoshida, Kazufumi; Fukunaga, Naoto; Koizumi, Shigeki; Nishiya, Kenta; Matsuda, Yasuhiro; Ishigami, Masanosuke; Nagasawa, Atsushi; Sakata, Ryuzo; Koyama, Tadaaki

    2017-03-01

    A 50-year-old man was admitted with fever and chill sensation 6 months ago. Transthoracic echocardiography (TTE) showed left and right coronary cusp prolapses and a thickened tissue of the aortic curtain. Congestive heart failure due to active infective aortic valve endocarditis was diagnosed, and he underwent aortic valve replacement. The aortic annulus was reconstructed using a glutaraldehydetreated autologous pericardium. Six months after surgery, TTE showed severe aortic regurgitation and saccular change in the aortic annulus. Transesophageal echocargiography showed some echo free space from left to noncoronary cusp and abnormal movement of the prosthetic valve annulus. Intraoperative examination showed dehiscence of the pericardial patch from the aortic wall, but no finding of infection. Aortic valve rereplacement was performed with reconstruction of the aortic annulus using a bovine pericardium. To prevent the dehiscence of the pericardial patch from the aortic wall, sutures fixing the prosthetic valve were passed from outside of the aortic wall.

  20. Stent graft implantation in an aortic pseudoaneurysm associated with a fractured Cheatham-Platinum stent in aortic coarctation.

    Science.gov (United States)

    Kuhelj, Dimitrij; Berden, Pavel; Podnar, Tomaž

    2016-03-01

    We report a case of aortic pseudoaneurysm associated with a fractured bare Cheatham-Platinum stent following stenting for aortic coarctation. These complications were recognised 6 years after the implantation procedure and were successfully managed by percutaneous stent graft implantation. Staged approach for stent dilatation might prevent development of aortic pseudoaneurysms. In addition, careful follow-up is warranted after stenting for aortic coarctation, particularly in patients with recognised aortic wall injury.

  1. Transitional features in human atherosclerosis. Intimal thickening, cholesterol clefts, and cell loss in human aortic fatty streaks.

    Science.gov (United States)

    Guyton, J. R.; Klemp, K. F.

    1993-01-01

    The possible transition from a subset of fatty streaks to fibrous plaques in human atherosclerosis has long been postulated, but transitional features in lesions have rarely been demonstrated. We examined human aortic fatty streaks to determine whether significant tendencies toward intimal thickening and toward deep extracellular lipid deposition might be found. To provide accurate ultrastructural assessment of lipid, tissues were processed by new electron microscopic cytochemical techniques. Unilateral fatty streaks exhibited a 60% increase in intimal thickness when compared to contralateral control tissue. Fat droplets in intimal cells accounted for approximately half of the increase; nonfat portions of cells and extracellular matrix accounted for the remainder. Six of 32 fatty streaks (19%) contained cholesterol clefts, which were found in the musculo-elastic (deep) layer of the intima or in the tunica media. Volume fractions occupied by cells in deep intima were reduced when cholesterol clefts were evident, suggesting loss of cells in early core regions. Light and electron microscopy showed structures consistent with lipid-rich core regions in lesions with cholesterol clefts and in a few lesions without cholesterol clefts. The findings of intimal thickening, core region formation, and disappearance of intimal cells constitute new evidence that some fatty streaks are progressive lesions and sites of eventual fibrous plaque development. The findings also suggest that the lipid-rich core region does not originate primarily from the debris of dead foam cells in the superficial intima, but instead arises from lipids accumulating gradually in the extracellular matrix of the deep intima. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:8238260

  2. wall

    Directory of Open Access Journals (Sweden)

    Irshad Kashif

    2016-01-01

    Full Text Available Maintaining indoor climatic conditions of buildings compatible with the occupant comfort by consuming minimum energy, especially in a tropical climate becomes a challenging problem for researchers. This paper aims to investigate this problem by evaluating the effect of different kind of Photovoltaic Trombe wall system (PV-TW on thermal comfort, energy consumption and CO2 emission. A detailed simulation model of a single room building integrated with PV-TW was modelled using TRNSYS software. Results show that 14-35% PMV index and 26-38% PPD index reduces as system shifted from SPV-TW to DGPV-TW as compared to normal buildings. Thermal comfort indexes (PMV and PPD lie in the recommended range of ASHARE for both DPV-TW and DGPV-TW except for the few months when RH%, solar radiation intensity and ambient temperature were high. Moreover PVTW system significantly reduces energy consumption and CO2 emission of the building and also 2-4.8 °C of temperature differences between indoor and outdoor climate of building was examined.

  3. High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells

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    Tang Rining

    2012-09-01

    Full Text Available Abstract Background Vascular calcification is one of the common complications in diabetes mellitus. Many studies have shown that high glucose (HG caused cardiovascular calcification, but its underlying mechanism is not fully understood. Recently, medial calcification has been most commonly described in the vessels of patients with diabetes. Chondrocytes were involved in the medial calcification. Recent studies have shown that the conversion into mesenchymal stem cells (MSCs via the endothelial-to-mesenchymal transition (EndMT could be triggered in chondrocytes. Our previous research has indicated that HG induced EndMT in human aortic endothelial cells (HAECs. Therefore, we addressed the question of whether HG-induced EndMT could be transitioned into MSCs and differentiated into chondrocytes. Methods HAECs were divided into three groups: a normal glucose (NG group, HG group (30 mmol/L, and mannitol (5.5 mmol/L NG + 24.5 mmol/L group. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of endothelial markers, such as CD31, and fibroblast markers, such as fibroblast-specific protein 1 (FSP-1. The expression of FSP-1 was detected by real time-PCR and western blots. Endothelial-derived MSCs were grown in MSC medium for one week. The expression of the MSCs markers STRO-1, CD44, CD10 and the chondrocyte marker SOX9 was detected by immunofluorescence staining and western blots. Chondrocyte expression was detected by alcian blue staining. Calcium deposits were analyzed by alizarin red staining. Results The incubation of HAECs exposed to HG resulted in a fibroblast-like phenotype. Double staining of the HAECs indicated a co-localization of CD31 and FSP-1. The expression of FSP-1 was significantly increased in the HG group, and the cells undergoing EndMT also expressed STRO-1, CD44 and SOX9 compared with the controls (P  Conclusions Our

  4. Nitric oxide production and inducible nitric oxide synthase protein expression in human abdominal aortic aneurysms and cultured aneurismal smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    LIAO Ming-fang; JING Zai-ping; BAO Jun-min; ZHAO Zhi-qing; MEI Zhi-jun; LU Qing-sheng; CUI Jia-sen; QU Le-feng; ZHANG Su-zhen

    2006-01-01

    Objective:To investigate the production of nitric oxide(NO) and the expression of inducible nitric oxide synthase (iNOS), and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by CochranMantel-Haenszel x2 test and Kendall correlation. Results: Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0.05) and the patients with occlusive arteries (P<0. 05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P<0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n= 20). There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall (Kendall coefficient = 0. 5032, P = 0. 0029). Conclusion:SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.

  5. Reverse Regulatory Pathway (H2S / PGE2 / MMP in Human Aortic Aneurysm and Saphenous Vein Varicosity.

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    Ingrid Gomez

    Full Text Available Hydrogen sulfide (H2S is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PGE2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2. This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA and thickening of saphenous vein (SV varicosities. The expression of the enzyme responsible for H2S synthesis, cystathionine-γ-lyase (CSE and its activity, were significantly higher in varicose vein as compared to SV. On the contrary, the endogenous H2S level and CSE expression were lower in AAA as compared to healthy aorta (HA. Endogenous H2S was responsible for inhibition of PGE2 synthesis mostly in varicose veins and HA. A similar effect was observed with exogenous H2S and consequently decreasing active MMP-1/TIMP ratios in SV and varicose veins. In contrast, in AAA, higher levels of PGE2 and active MMP-1/TIMP ratios were found versus HA. These findings suggest that differences in H2S content in AAA and varicose veins modulate endogenous PGE2 production and consequently the MMP/TIMP ratio. This mechanism may be crucial in vascular wall remodeling observed in different vascular pathologies (aneurysm, varicosities, atherosclerosis and pulmonary hypertension.

  6. Reverse Regulatory Pathway (H2S / PGE2 / MMP) in Human Aortic Aneurysm and Saphenous Vein Varicosity.

    Science.gov (United States)

    Gomez, Ingrid; Ozen, Gulsev; Deschildre, Catherine; Amgoud, Yasmine; Boubaya, Lilia; Gorenne, Isabelle; Benyahia, Chabha; Roger, Thomas; Lesèche, Guy; Galardon, Erwan; Topal, Gokce; Jacob, Marie-Paule; Longrois, Dan; Norel, Xavier

    2016-01-01

    Hydrogen sulfide (H2S) is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PG)E2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP) activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2). This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA) and thickening of saphenous vein (SV) varicosities. The expression of the enzyme responsible for H2S synthesis, cystathionine-γ-lyase (CSE) and its activity, were significantly higher in varicose vein as compared to SV. On the contrary, the endogenous H2S level and CSE expression were lower in AAA as compared to healthy aorta (HA). Endogenous H2S was responsible for inhibition of PGE2 synthesis mostly in varicose veins and HA. A similar effect was observed with exogenous H2S and consequently decreasing active MMP-1/TIMP ratios in SV and varicose veins. In contrast, in AAA, higher levels of PGE2 and active MMP-1/TIMP ratios were found versus HA. These findings suggest that differences in H2S content in AAA and varicose veins modulate endogenous PGE2 production and consequently the MMP/TIMP ratio. This mechanism may be crucial in vascular wall remodeling observed in different vascular pathologies (aneurysm, varicosities, atherosclerosis and pulmonary hypertension).

  7. Active Smoking Increases Microsomal PGE2-Synthase-1/PGE-Receptor-4 Axis in Human Abdominal Aortic Aneurysms

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    Jaime-Félix Dilmé

    2014-01-01

    Full Text Available Background. The cyclooxygenase- (COX- 2/microsomal PGE-synthase- (mPGES- 1/PGE-receptor- (EP- 4 axis could play a key role in the physiopathology of abdominal aortic aneurysm (AAA in humans. In this study, we investigated the influence of cardiovascular risk factors on the expression of the PGE2 pathway in human AAA. Methods. Aortic (n=89 and plasma (n=79 samples from patients who underwent AAA repair were collected. Patients were grouped according to risk factors. COX-isoenzymes, mPGES-1, EPs, α-actin, and CD45 and CD68 transcripts levels were quantified by QRT-PCR and plasma PGE2 metabolites by EIA. Results. Current smoking (CS patients compared to no-CS had significantly higher local levels of mPGES-1 (P=0.009, EP-4 (P=0.007, and PGE2 metabolites plasma levels (P=0.008. In the multiple linear regression analysis, these parameters remained significantly enhanced in CS after adding confounding factors. Results from association studies with cell type markers suggested that the increased mPGES-1/EP-4 levels were mainly associated with microvascular endothelial cells. Conclusions. This study shows that elements of the PGE2 pathway, which play an important role in AAA development, are increased in CS. These results provide insight into the relevance of tobacco smoking in AAA development and reinforce the potential of mPGES-1 and EP-4 as targets for therapy in AAA patients.

  8. Active smoking increases microsomal PGE2-synthase-1/PGE-receptor-4 axis in human abdominal aortic aneurysms.

    Science.gov (United States)

    Dilmé, Jaime-Félix; Solà-Villà, David; Bellmunt, Sergi; Romero, José-María; Escudero, José-Román; Camacho, Mercedes; Vila, Luis

    2014-01-01

    The cyclooxygenase- (COX-) 2/microsomal PGE-synthase- (mPGES-) 1/PGE-receptor- (EP-) 4 axis could play a key role in the physiopathology of abdominal aortic aneurysm (AAA) in humans. In this study, we investigated the influence of cardiovascular risk factors on the expression of the PGE2 pathway in human AAA. Aortic (n = 89) and plasma (n = 79) samples from patients who underwent AAA repair were collected. Patients were grouped according to risk factors. COX-isoenzymes, mPGES-1, EPs, α-actin, and CD45 and CD68 transcripts levels were quantified by QRT-PCR and plasma PGE2 metabolites by EIA. Current smoking (CS) patients compared to no-CS had significantly higher local levels of mPGES-1 (P = 0.009), EP-4 (P = 0.007), and PGE2 metabolites plasma levels (P = 0.008). In the multiple linear regression analysis, these parameters remained significantly enhanced in CS after adding confounding factors. Results from association studies with cell type markers suggested that the increased mPGES-1/EP-4 levels were mainly associated with microvascular endothelial cells. This study shows that elements of the PGE2 pathway, which play an important role in AAA development, are increased in CS. These results provide insight into the relevance of tobacco smoking in AAA development and reinforce the potential of mPGES-1 and EP-4 as targets for therapy in AAA patients.

  9. Isoflavone genistein protects high glucose-induced human aortic endothelial cell apoptosis through estrogen receptor-mediated pathway

    Institute of Scientific and Technical Information of China (English)

    Wenwen Zhong; Yang Liu; Guang Yang; Hui Tian

    2008-01-01

    Objective The aim of this study was to determine if isoflavone genistien has protective effects against high glucose-induced cell apoptosis in human aortic endlthelial cells,and investigate the possible mechanism for this protection.Methods Human aortic endothelial cells subjected to normal (5mmol/L) or high glucose (25mmol/L) were treated with genistein at 0,50,100nmol/L.Parallel experiments were performed with 100nM 17b-estradiol,and also in the presence and absence of the pure anti-estrogen ICI-182,780 (100nmol/L).The effects on cell apoptotic DNA fragmentation were determined using cell death ELISA,and the effects on cellular proliferation were determined using tritiated thymidine incorporation assay.Estrogen receptor expression was detected by Taqman quantitative PCR.Results Genistein at 100nmol/L significantly reduced high glucose-induced DNA fragmentation,and reversed cell DNA synthesis inhibition (P<0.001) after 24 hours' incubation.The effect of genistein was completely blocked by ICI-182,780administration.Estrogen receptor beta,but not alpha was found to be expressed in these cells.Conclusion Isoflavone genistein shows protection against high glucose-induced cell damage through estrogen receptor beta,reducing apoptotic DNA damage and protecting from the inhibition of cell proliferation.

  10. Resolving Low-Density Lipoprotein (LDL) on the Human Aortic Surface Using Large Eddy Simulation

    Science.gov (United States)

    Lantz, Jonas; Karlsson, Matts

    2011-11-01

    The prediction and understanding of the genesis of vascular diseases is one of the grand challenges in biofluid engineering. The progression of atherosclerosis is correlated to the build- up of LDL on the arterial surface, which is affected by the blood flow. A multi-physics simulation of LDL mass transport in the blood and through the arterial wall of a subject specific human aorta was performed, employing a LES turbulence model to resolve the turbulent flow. Geometry and velocity measurements from magnetic resonance imaging (MRI) were incorporated to assure physiological relevance of the simulation. Due to the turbulent nature of the flow, consecutive cardiac cycles are not identical, neither in vivo nor in the simulations. A phase average based on a large number of cardiac cycles is therefore computed, which is the proper way to get reliable statistical results from a LES simulation. In total, 50 cardiac cycles were simulated, yielding over 2.5 Billion data points to be post-processed. An inverse relation between LDL and WSS was found; LDL accumulated on locations where WSS was low and vice-versa. Large temporal differences were present, with the concentration level decreasing during systolic acceleration and increasing during the deceleration phase. This method makes it possible to resolve the localization of LDL accumulation in the normal human aorta with its complex transitional flow.

  11. Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

    NARCIS (Netherlands)

    Zeng, Q.; Song, R.; Fullerton, D.A.; Ao, L.; Zhai, Y.; Li, S.; Ballak, D.B.; Cleveland, J.C., Jr.; Reece, T.B.; McKinsey, T.A.; Xu, D.; Dinarello, C.A.; Meng, X.

    2017-01-01

    Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased h

  12. Modification of the secretion pattern of proteases, inflammatory mediators, and extracellular matrix proteins by human aortic valve is key in severe aortic stenosis.

    Science.gov (United States)

    Alvarez-Llamas, Gloria; Martín-Rojas, Tatiana; de la Cuesta, Fernando; Calvo, Enrique; Gil-Dones, Felix; Dardé, Veronica M; Lopez-Almodovar, Luis F; Padial, Luis R; Lopez, Juan-Antonio; Vivanco, Fernando; Barderas, Maria G

    2013-09-01

    One of the major challenges in cardiovascular medicine is to identify candidate biomarker proteins. Secretome analysis is particularly relevant in this search as it focuses on a subset of proteins released by a cell or tissue under certain conditions. The sample can be considered as a plasma subproteome and it provides a more direct approximation to the in vivo situation. Degenerative aortic stenosis is the most common worldwide cause of valve replacement. Using a proteomic analysis of the secretome from aortic stenosis valves we could identify candidate markers related to this pathology, which may facilitate early diagnosis and treatment. For this purpose, we have designed a method to validate the origin of secreted proteins, demonstrating their synthesis and release by the tissue and ruling out blood origin. The nLC-MS/MS analysis showed the labeling of 61 proteins, 82% of which incorporated the label in only one group. Western blot and selective reaction monitoring differential analysis, revealed a notable role of the extracellular matrix. Variation in particular proteins such as PEDF, cystatin and clusterin emphasizes the link between aortic stenosis and atherosclerosis. In particular, certain proteins variation in secretome levels correlates well, not only with label incorporation trend (only labeled in aortic stenosis group) but, more importantly, with alterations found in plasma from an independent cohort of samples, pointing to specific candidate markers to follow up in diagnosis, prognosis, and therapeutic intervention.

  13. Transcatheter aortic valve implantation with the NVT Allegra transcatheter heart valve system: first-in-human experience with a novel self-expanding transcatheter heart valve.

    Science.gov (United States)

    Wenaweser, Peter; Stortecky, Stefan; Schütz, Torsten; Praz, Fabien; Gloekler, Steffen; Windecker, Stephan; Elsässer, Albrecht

    2016-05-17

    We aimed to demonstrate the feasibility and investigate the safety of a novel, self-expanding trans-catheter heart valve in a selected patient population with severe aortic stenosis. Between January and September 2013, a total of 21 patients with symptomatic severe aortic stenosis were eligible for transcatheter aortic valve implantation (TAVI) with the self-expanding NVT Allegra bioprosthesis (New Valve Technology, Hechingen, Germany) at two cardiovascular centres. Patients were elderly (age 83.8±4 years), predominantly female (95.2%), and all were considered to be at prohibitive risk for surgical aortic valve replacement (logistic EuroSCORE 30.4±11%). Procedural and device success was achieved in 95.2% and 85.7%, respectively. Echocardiographic assessment at discharge showed favourable haemodynamic results with a reduction of the mean transvalvular aortic gradient from 48.0±21 mmHg to 8.9±3 mmHg. In the majority of patients (90.5%), none or trace aortic regurgitation was recorded. Permanent pacemaker implantation was required in 23.8% of patients within the first 30 days of follow-up. Apart from one procedural death, no other serious adverse events were observed during the periprocedural period. TAVI with the NVT Allegra system was highly effective in alleviating symptoms and reducing NYHA functional class at 30-day follow-up. The first-in-human experience with the NVT Allegra transcatheter heart valve prosthesis was associated with a high rate of procedural success. Furthermore, the NVT Allegra bioprosthesis was able to achieve favourable haemodynamic results and effectively alleviate symptoms at 30-day follow-up. The larger, multicentre NAUTILUS study will provide further information on the safety and efficacy of this novel, second-generation transcatheter aortic bioprosthesis.

  14. Pathogen recognition by Toll-like receptor 2 activates Weibel-Palade body exocytosis in human aortic endothelial cells.

    Science.gov (United States)

    Into, Takeshi; Kanno, Yosuke; Dohkan, Jun-ichi; Nakashima, Misako; Inomata, Megumi; Shibata, Ken-ichiro; Lowenstein, Charles J; Matsushita, Kenji

    2007-03-16

    The endothelial cell-specific granule Weibel-Palade body releases vasoactive substances capable of modulating vascular inflammation. Although innate recognition of pathogens by Toll-like receptors (TLRs) is thought to play a crucial role in promotion of inflammatory responses, the molecular basis for early-phase responses of endothelial cells to bacterial pathogens has not fully been understood. We here report that human aortic endothelial cells respond to bacterial lipoteichoic acid (LTA) and synthetic bacterial lipopeptides, but not lipopolysaccharide or peptidoglycan, to induce Weibel-Palade body exocytosis, accompanied by release or externalization of the storage components von Willebrand factor and P-selectin. LTA could activate rapid Weibel-Palade body exocytosis through a TLR2- and MyD88-dependent mechanism without de novo protein synthesis. This process was at least mediated through MyD88-dependent phosphorylation and activation of phospholipase Cgamma. Moreover, LTA activated interleukin-1 receptor-associated kinase-1-dependent delayed exocytosis with de novo protein synthesis and phospholipase Cgamma-dependent activation of the NF-kappaB pathway. Increased TLR2 expression by transfection or interferon-gamma treatment increased TLR2-mediated Weibel-Palade body exocytosis, whereas reduced TLR2 expression under laminar flow decreased the response. Thus, we propose a novel role for TLR2 in induction of a primary proinflammatory event in aortic endothelial cells through Weibel-Palade body exocytosis, which may be an important step for linking innate recognition of bacterial pathogens to vascular inflammation.

  15. Aortic biomechanics in hypertrophic cardiomyopathy

    Science.gov (United States)

    Badran, Hala Mahfouz; Soltan, Ghada; Faheem, Nagla; Elnoamany, Mohamed Fahmy; Tawfik, Mohamed; Yacoub, Magdi

    2015-01-01

    Background: Ventricular-vascular coupling is an important phenomenon in many cardiovascular diseases. The association between aortic mechanical dysfunction and left ventricular (LV) dysfunction is well characterized in many disease entities, but no data are available on how these changes are related in hypertrophic cardiomyopathy (HCM). Aim of the work: This study examined whether HCM alone is associated with an impaired aortic mechanical function in patients without cardiovascular risk factors and the relation of these changes, if any, to LV deformation and cardiac phenotype. Methods: 141 patients with HCM were recruited and compared to 66 age- and sex-matched healthy subjects as control group. Pulse pressure, aortic strain, stiffness and distensibility were calculated from the aortic diameters measured by M-mode echocardiography and blood pressure obtained by sphygmomanometer. Aortic wall systolic and diastolic velocities were measured using pulsed wave Doppler tissue imaging (DTI). Cardiac assessment included geometric parameters and myocardial deformation (strain and strain rate) and mechanical dyssynchrony. Results: The pulsatile change in the aortic diameter, distensibility and aortic wall systolic velocity (AWS') were significantly decreased and aortic stiffness index was increased in HCM compared to control (P < .001) In HCM AWS' was inversely correlated to age(r = − .32, P < .0001), MWT (r = − .22, P < .008), LVMI (r = − .20, P < .02), E/Ea (r = − .16, P < .03) LVOT gradient (r = − 19, P < .02) and severity of mitral regurg (r = − .18, P < .03) but not to the concealed LV deformation abnormalities or mechanical dyssynchrony. On multivariate analysis, the key determinant of aortic stiffness was LV mass index and LVOT obstruction while the role LV dysfunction in aortic stiffness is not evident in this population. Conclusion: HCM is associated with abnormal aortic mechanical properties. The severity of cardiac

  16. Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

    Science.gov (United States)

    Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

    2016-02-01

    Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

  17. Impact of exercise training on arterial wall thickness in humans.

    NARCIS (Netherlands)

    Thijssen, D.H.J.; Cable, N.T.; Green, D.J.

    2012-01-01

    Thickening of the carotid artery wall has been adopted as a surrogate marker of pre-clinical atherosclerosis, which is strongly related to increased cardiovascular risk. The cardioprotective effects of exercise training, including direct effects on vascular function and lumen dimension, have been co

  18. Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells

    Directory of Open Access Journals (Sweden)

    Groscurth Peter

    2008-02-01

    Full Text Available Abstract Background Atherosclerosis is still the leading cause of death in the western world. Besides known risk factors studies demonstrating Chlamydophila pneumoniae (C. pneumoniae to be implicated in the progression of the disease, little is known about C. pneumoniae infection dynamics. We investigated whether C. pneumoniae induce cell death of human aortic endothelial cells, a cell type involved in the initiation of atherosclerosis, and whether chlamydial spots derive from inclusions. Results Lactate dehydrogenase release revealed host cell death to be dependent on the amounts of Chlamydia used for infection. The morphology of lysed human aortic endothelial cells showed DNA strand breaks simultaneously with cell membrane damage exclusively in cells carrying Chlamydia as spots. Further ultrastructural analysis revealed additional organelle dilation, leading to the definition as aponecrotic cell death of endothelial cells. Exclusive staining of the metabolic active pathogens by chlamydial heat shock protein 60 labelling and ceramide incorporation demonstrated that the bacteria responsible for the induction of aponecrosis had resided in former inclusions. Furthermore, a strong pro-inflammatory molecule, high mobility group box protein 1, was shown to be released from aponecrotic host cells. Conclusion From the data it can be concluded that aponecrosis inducing C. pneumoniae stem from inclusions, since metabolically active bacterial spots are strongly associated with aponecrosis late in the infectious cycle in vascular endothelial cells and metabolic activity was exclusively located inside of inclusions in intact cells. Vice versa initial spot-like infection with metabolically inert bacteria does not have an effect on cell death induction. Hence, C. pneumoniae infection can contribute to atherosclerosis by initial endothelial damage.

  19. Increased transcript level of poly(ADP-ribose) polymerase (PARP-1) in human tricuspid compared with bicuspid aortic valves correlates with the stenosis severity

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Edit, E-mail: edit.nagy@karolinska.se [Department of Medicine, Karolinska Institutet, Stockholm (Sweden); Department of Cardiology, Karolinska University Hospital, Stockholm (Sweden); Caidahl, Kenneth [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Clinical Physiology, Karolinska University Hospital, Stockholm (Sweden); Franco-Cereceda, Anders [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Throracic Surgery, Karolinska University Hospital, Stockholm (Sweden); Baeck, Magnus [Department of Medicine, Karolinska Institutet, Stockholm (Sweden); Department of Cardiology, Karolinska University Hospital, Stockholm (Sweden)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. Black-Right-Pointing-Pointer We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. Black-Right-Pointing-Pointer Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. Black-Right-Pointing-Pointer The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. Black-Right-Pointing-Pointer Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C{sub 4} (LTC{sub 4}) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = -0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = -0.498; P = 0.0298) only in tricuspid aortic valves

  20. Aortic stenosis

    Science.gov (United States)

    ... Images Aortic stenosis Heart valves References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/ ...

  1. Abdominal Aortic Aneurysm (AAA)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Abdominal Aortic Aneurysm (AAA) Abdominal aortic aneurysm (AAA) occurs when atherosclerosis ... an abdominal aortic aneurysm treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, ...

  2. Structural valve deterioration after aortic valve replacement with Medtronic freestyle stentless porcine aortic root bioprostheses.

    Science.gov (United States)

    Nishida, Hidefumi; Komiya, Tatsuhiko; Sakaguchi, Genichi; Shimamoto, Takeshi

    2014-01-01

    The Medtronic freestyle aortic root bioprosthesis (Medtronic, Inc., Minneapolis, MN, USA) is a stentless valve with an effective orifice area that is larger than that observed on other bioprostheses. However, there have been sporadic reports of structural valve deterioration (SVD), such as aortic root wall rupture, leaflet tearing, and pseudoaneurysm formation. We report five cases of SVD of freestyle aortic root bioprostheses. © 2013 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals, Inc.

  3. Synergy between sphingosine 1-phosphate and lipopolysaccharide signaling promotes an inflammatory, angiogenic and osteogenic response in human aortic valve interstitial cells.

    Directory of Open Access Journals (Sweden)

    Isabel Fernández-Pisonero

    Full Text Available Given that the bioactive lipid sphingosine 1-phosphate is involved in cardiovascular pathophysiology, and since lipid accumulation and inflammation are hallmarks of calcific aortic stenosis, the role of sphingosine 1-phosphate on the pro-inflammatory/pro-osteogenic pathways in human interstitial cells from aortic and pulmonary valves was investigated. Real-time PCR showed sphingosine 1-phosphate receptor expression in aortic valve interstitial cells. Exposure of cells to sphingosine 1-phosphate induced pro-inflammatory responses characterized by interleukin-6, interleukin-8, and cyclooxygenase-2 up-regulations, as observed by ELISA and Western blot. Strikingly, cell treatment with sphingosine 1-phosphate plus lipopolysaccharide resulted in the synergistic induction of cyclooxygenase-2, and intercellular adhesion molecule 1, as well as the secretion of prostaglandin E2, the soluble form of the intercellular adhesion molecule 1, and the pro-angiogenic factor vascular endothelial growth factor-A. Remarkably, the synergistic effect was significantly higher in aortic valve interstitial cells from stenotic than control valves, and was drastically lower in cells from pulmonary valves, which rarely undergo stenosis. siRNA and pharmacological analysis revealed the involvement of sphingosine 1-phosphate receptors 1/3 and Toll-like receptor-4, and downstream signaling through p38/MAPK, protein kinase C, and NF-κB. As regards pro-osteogenic pathways, sphingosine 1-phosphate induced calcium deposition and the expression of the calcification markers bone morphogenetic protein-2 and alkaline phosphatase, and enhanced the effect of lipopolysaccharide, an effect that was partially blocked by inhibition of sphingosine 1-phosphate receptors 3/2 signaling. In conclusion, the interplay between sphingosine 1-phosphate receptors and Toll-like receptor 4 signaling leads to a cooperative up-regulation of inflammatory, angiogenic, and osteogenic pathways in aortic valve

  4. Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Zhou, Yi; Wu, Wenxue; Lindholt, Jes S

    2015-01-01

    AIMS: Regulatory T cells (Tregs) protect mice from angiotensin II (Ang-II)-induced abdominal aortic aneurysms (AAA). This study tested whether AAA patients are Treg-insufficient and the Treg molecular mechanisms that control AAA pathogenesis. METHODS AND RESULTS: ELISA determined the Foxp3...... concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P AAA annual expansion rate before...... (r = -0.147, P = 0.007) and after (r = -0.153, P = 0.006) adjustment for AAA risk factors. AAA in apolipoprotein E-deficient (Apoe(-/-)) mice that received different doses of Ang-II exhibited a negative correlation of lesion Foxp3(+) Treg numbers with AAA size (r = -0.883, P

  5. Ang II enhances noradrenaline release from sympathetic nerve endings thus contributing to the up-regulation of metalloprotease-2 in aortic dissection patients' aorta wall.

    Directory of Open Access Journals (Sweden)

    Zhipeng Hu

    Full Text Available OBJECT: To test the hypothesis that angiotensin II (Ang II could enhance noradrenaline (NA release from sympathetic nerve endings of the aorta thus contributing to the up-regulation of matrix metalloproteinase 2 (MMP-2 during the formation of aortic dissection (AD. METHODS: Ang II, NA, MMP-2, MMP-9 of the aorta sample obtained during operation from aortic dissection patients were detected by High Performance Liquid Chromatography and ELISA and compared with controls. Isotope labelling method was used to test the impact of exogenous Ang II and noradrenaline on the NA release and MMP-2, MMP-9 expression on Sprague Dawley (SD rat aorta rings in vitro. Two kidneys, one clip, models were replicated for further check of that impact in SD rats in vivo. RESULTS: The concentration of Ang II, MMP-2, 9 was increased and NA concentration was decreased in aorta samples from AD patients. Exogenous Ang II enhanced while exogenous NA restrained NA release from aortic sympathetic endings. The Ang II stimulated NA release and the following MMP-2 up-regulation could be weakened by Losartan and chemical sympathectomy. Beta blocker did not influence NA release but down-regulated MMP-2. Long term in vivo experiments confirmed that Ang II could enhance NA release and up-regulate MMP-2. CONCLUSIONS: AD is initiated by MMP-2 overexpression as a result of increased NA release from sympathetic nervous endings in response to Ang II. This indicates an interaction of RAS and SAS during the formation of AD.

  6. Architectural and morphological assessment of rat abdominal wall muscles: comparison for use as a human model.

    Science.gov (United States)

    Brown, Stephen H M; Banuelos, Karina; Ward, Samuel R; Lieber, Richard L

    2010-09-01

    The abdominal wall is a composite of muscles that are important for the mechanical stability of the spine and pelvis. Tremendous clinical attention is given to these muscles, yet little is known about how they function in isolation or how they interact with one another. Given the morphological, vascular, and innervation complexities associated with these muscles and their proximity to the internal organs, an appropriate animal model is important for understanding their physiological and mechanical significance during function. To determine the extent to which the rat abdominal wall resembles that of human, 10 adult male Sprague-Dawley rats were killed and formalin-fixed for architectural and morphological analyses of the four abdominal wall muscles (rectus abdominis, external oblique, internal oblique, and transversus abdominis). Physiological cross-sectional areas and optimal fascicle lengths demonstrated a pattern that was similar to human abdominal wall muscles. In addition, sarcomere lengths measured in the neutral spine posture were similar to human in their relation to optimal sarcomere length. These data indicate that the force-generating and length change capabilities of these muscles, relative to one another, are similar in rat and human. Finally, the fiber lines of action of each abdominal muscle were similar to human over most of the abdominal wall. The main exception was in the lower abdominal region (inferior to the pelvic crest), where the external oblique becomes aponeurotic in human but continues as muscle fibers into its pelvic insertion in the rat. We conclude that, based on the morphology and architecture of the abdominal wall muscles, the adult male Sprague-Dawley rat is a good candidate for a model representation of human, particularly in the middle and upper abdominal wall regions.

  7. Evaluation of inflammatory cells in abdominal aortic aneurysmal wall by tomography emission positron; Anevrisme de l aorte abdominale et inflammation vasculaire: place de la tomographie par emission de positons

    Energy Technology Data Exchange (ETDEWEB)

    Sakalihasan, N. [Service de chirurgie cardiovasculaire et thoracique, CHU de liege, domaine universitaire du Sart Tilman, batimant B-35, 4000 liege 1, (Belgium); Hustinx, R. [Service de medecine nucleaire, CHU de Liege, (Belgium); Gomez, P.; Defraigne, J.O. [Departement de medecine nucleaire, CHU de Liege, (Belgium)

    2009-05-15

    The objective was to identify the methods of functional imaging and the molecular markers that could help to predict the imminence of a rupture in abdominal aortic aneurysm. The potential of the PET was studied to detect a hyper-metabolic state in the aneurysm wall and this information was connected with the evolution of the disease. An uptake of F.D.G. in the aneurysm wall reflects the presence of a great density of inflammatory cells (macrophages, lymphocytes, polymorphonuclear cells). It has been observed an accumulation of polymorphonuclear cells accompanying a dense infiltration of macrophages and lymphocytes only in the site of break. Our preliminary study and our most recent observations (not yet published) suggest a possible relationship between the F.G.D. captation by the aneurysm wall and the start of the activity of the matrix metallo-proteinases leading to the break. The PET scan could be useful for high risk patients because a positive PET imaging stigmatizes a greater risk of break. consequently, the positive PET imaging represents a diagnosis argument to proceed to a surgical operation, despite the age of the patient, the size of the abdominal aorta aneurysm and the higher operative risk. however, more data to better define the criteria of using the PET/T.D.M. in the evaluation of abdominal aorta aneurysm and to determine its exact contribution in the treatment determination. (N.C.)

  8. Adventitial vasa vasorum arteriosclerosis in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Hiroki Tanaka

    Full Text Available Abdominal aortic aneurysm (AAA is a common disease among elderly individuals. However, the precise pathophysiology of AAA remains unknown. In AAA, an intraluminal thrombus prevents luminal perfusion of oxygen, allowing only the adventitial vaso vasorum (VV to deliver oxygen and nutrients to the aortic wall. In this study, we examined changes in the adventitial VV wall in AAA to clarify the histopathological mechanisms underlying AAA. We found marked intimal hyperplasia of the adventitial VV in the AAA sac; further, immunohistological studies revealed proliferation of smooth muscle cells, which caused luminal stenosis of the VV. We also found decreased HemeB signals in the aortic wall of the sac as compared with those in the aortic wall of the neck region in AAA. The stenosis of adventitial VV in the AAA sac and the malperfusion of the aortic wall observed in the present study are new aspects of AAA pathology that are expected to enhance our understanding of this disease.

  9. Leukotriene B4 levels in human atherosclerotic plaques and abdominal aortic aneurysms.

    Directory of Open Access Journals (Sweden)

    Pleunie van den Borne

    Full Text Available BACKGROUND: Leukotriene B4 (LTB4 has been associated with the initiation and progression of atherosclerosis and abdominal aortic aneurysm (AAA formation. However, associations of LTB4 levels with tissue characteristics and adverse clinical outcome of advanced atherosclerosis and AAA are scarcely studied. We hypothesized that LTB4 levels are associated with a vulnerable plaque phenotype and adverse clinical outcome. Furthermore, that LTB4 levels are associated with inflammatory AAA and adverse clinical outcome. METHODS: Atherosclerotic plaques and AAA specimens were selected from two independent databases for LTB4 measurements. Plaques were isolated during carotid endarterectomy from asymptomatic (n = 58 or symptomatic (n = 317 patients, classified prior to surgery. LTB4 levels were measured without prior lipid extraction and levels were corrected for protein content. LTB4 levels were related to plaque phenotype, baseline patient characteristics and clinical outcome within three years following surgery. Seven non-diseased mammary artery specimens served as controls. AAA specimens were isolated during open repair, classified as elective (n = 189, symptomatic (n = 29 or ruptured (n = 23. LTB4 levels were measured similar to the plaque measurements and were related to tissue characteristics, baseline patient characteristics and clinical outcome. Twenty-six non-diseased aortic specimens served as controls. RESULTS: LTB4 levels corrected for protein content were not significantly associated with histological characteristics specific for vulnerable plaques or inflammatory AAA as well as clinical presentation. Moreover, it could not predict secondary manifestations independently investigated in both databases. However, LTB4 levels were significantly lower in controls compared to plaque (p = 0.025 or AAA (p = 0.017. CONCLUSIONS: LTB4 levels were not associated with a vulnerable plaque phenotype or inflammatory AAA or clinical

  10. Influence of virtual intervention and blood rheology on mass transfer through thoracic aortic aneurysm.

    Science.gov (United States)

    Lei, Yu; Chen, Ming; Xiong, Guanglei; Chen, Jie

    2015-09-18

    Computational fluid dynamics tools have been used to investigate blood flow through the human thoracic aortic models with aneurysm before and after virtual stent graft operation. The impact of blood rheology and aortic geometry on the wall shear stress (WSS), luminal surface low-density lipoproteins (LDL) concentration, and oxygen flux along the arterial wall is investigated. The stent graft at the aneurysm has significant effects on WSS and mass transport in blood flow. Due to the low flow rate, Newtonian blood assumption generally under-estimates the WSS. The non-Newtonian blood rheology play an important role in the LDL transport as well as oxygen transport. It is found that WSS alone is insufficient to correctly predict the location with high risk of atherogenesis. The results suggest that WSS, luminal surface LDL concentration, and the oxygen flux on the wall have to be considered together to evaluate the performance of virtual operation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

    Science.gov (United States)

    Carrion, Katrina; Dyo, Jeffrey; Patel, Vishal; Sasik, Roman; Mohamed, Salah A; Hardiman, Gary; Nigam, Vishal

    2014-01-01

    Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.

  12. Role of chemical elements in formation of an aortic aneurysm.

    Science.gov (United States)

    Okuneva, G N; Levicheva, E N; Loginova, I Iu; Volkov, A M; Cherniavskiĭ, A M; Al'sov, S A; Trunova, V A; Zvereva, V V

    2008-01-01

    The method of X-ray fluorescence employing synchronous radiation was used to study the content of chemical elements (CE) in the aortic wall in patients suffering from CAD (Group I), patients diagnosed with an ascending aortic aneurysm (Group II), and those presenting with aortic dissection (Group III). The obtained findings revealed a pronounced CE disbalance in the aortic wall in Group II and III patients as compared with Group I patients, suggesting an important role of trace and macroelements in metabolic processes related to formation of artic aneurysms. Based on the degree of the ascending aorta dilatation, we determined the coefficient of the ratio of the ascending aorta maximal diameter to the fibrous ring aortic valve diameter, equalling 1.88 +/- 0.04, above which metabolic processes in the aortic wall change over to a qualitatively another level. This point was arbitrarily termed the metabolic process reversibility point.

  13. [Aortic aneurysm].

    Science.gov (United States)

    Villar, Fernando; Pedro-Botet, Juan; Vila, Ramón; Lahoz, Carlos

    2013-01-01

    Aortic aneurysm is one important cause of death in our country. The prevalence of abdominal aortic aneurism (AAA) is around 5% for men older than 50 years of age. Some factors are associated with increased risk for AAA: age, hypertension, hypercholesterolemia, cardiovascular disease and, in particular, smoking. The medical management of patients with an AAA includes cardiovascular risk treatment, particularly smoking cessation. Most of major societies guidelines recommend ultrasonography screening for AAA in men aged 65 to 75 years who have ever smoked because it leads to decreased AAA-specific mortality. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  14. MicroRNAs, fibrotic remodeling, and aortic aneurysms

    Science.gov (United States)

    Milewicz, Dianna M.

    2012-01-01

    Aortic aneurysms are a common clinical condition that can cause death due to aortic dissection or rupture. The association between aortic aneurysm pathogenesis and altered TGF-β signaling has been the subject of numerous investigations. Recently, a TGF-β–responsive microRNA (miR), miR-29, has been identified to play a role in cellular phenotypic modulation during aortic development and aging. In this issue of JCI, Maegdefessel and colleagues demonstrate that decreasing the levels of miR-29b in the aortic wall can attenuate aortic aneurysm progression in two different mouse models of abdominal aortic aneurysms. This study highlights the relevance of miR-29b in aortic disease but also raises questions about its specific role. PMID:22269322

  15. A technique of aortic annulus enlargement with a Freestyle stentless bioprosthesis.

    Science.gov (United States)

    Bical, Olivier M; Nutu, Ovidiu; Deleuze, Philippe

    2012-02-01

    We describe our surgical technique to manage a small aortic annulus during aortic valve replacement. Starting with the posterior annular enlargement incision described by Manouguian, a stentless porcine aortic root, with excision of the left and right porcine coronary segments and conservation of the mural wall (Freestyle MS design, Medtronic, Minneapolis, MN ), was used. The Freestyle bioprosthesis enlarges the aortic annulus using a direct suture of the valve on the enlarged annulus, and the aorta is closed by a direct suture of the mural wall of the bioprosthesis. Therefore, the aortic annulus enlargement is made only using the aortic bioprosthesis, without other material.

  16. Infected abdominal aortic aneurysm due to Morganella morganii: CT findings.

    Science.gov (United States)

    Kwon, Oh Young; Lee, Jong Seok; Choi, Han Sung; Hong, Hoon Pyo; Ko, Young Gwan

    2011-02-01

    An infected aortic aneurysm, or mycotic aneurysm, is a rare arterial dilatation due to destruction of the infected vessel wall. Common pathogens resulting in an infected aortic aneurysm are Salmonella and Clostridium species, as well as Staphylococcus aureus; Morganella morganii, on the other hand, is very rare. An infected abdominal aortic aneurysm has tendencies to grow rapidly and to rupture. The mortality rate is high in patients undergoing emergent surgical intervention. We report the case of a 65-year-old man who presented with an infected abdominal aortic aneurysm caused by M. morganii. A high index of suspicion and imaging tests are necessary in order to diagnose an infected aortic aneurysm.

  17. Treatment of infrarenal abdominal aortic dissection concomitant with an aneurysm

    Institute of Scientific and Technical Information of China (English)

    WANG Li-xin; ZHU Ting; FU Wei-guo; WANG Yu-qi; XI Xun; GUO Da-qiao; CHEN Bin; JIANG Jun-hao; YANG Ju; SHI Zhen-yu

    2007-01-01

    @@ Aortic dissection occurs when layers of the aortic walls are separated by the blood flow through an intimal tear. Dissection of the aorta most frequently originates in the ascending aorta (70%), followed by the descending aorta (22%), the aortic arch (7%) and the abdominal aorta (1/%).1 The dissection limited to the abdominal aorta is rare.2 An isolated abdominal aortic dissection (IAAD) concomitant with an abdominal aortic aneurysm (AAA) is uncommon. We present here one patient with IAAD and AAA treated by endovascular therapy.

  18. Screening aortic drug treatments through arterial compliance measurements.

    Science.gov (United States)

    Rentschler, Mark E; Baxter, B Timothy

    2008-10-01

    Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic diameter increases in association with a complex remodeling process that includes changes in the structure and content of key proteins, elastin and collagen. As these changes occur, the tissue mechanical properties also change. The natural history of AAA is progressive enlargement to a point of mechanical tissue failure typically followed by death. Currently, the marker used to predict the risk of impending rupture is the largest transverse diameter. After reaching a diameter threshold of 5.5 cm the AAA needs to be surgically repaired. This criterion does not consider any patient-specific information or heterogeneity of the AAA that may, in some cases, lead to rupture before the AAA reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. While no medical treatment is yet approved, doxycycline (Doxy) has been shown to greatly reduce AAA growth in animal models and has been shown to slow growth in 1 small clinical trial. While larger prospective randomized trials are needed, one unknown is what effect Doxy has on the structural integrity of the aortic wall. That is, does slowed AAA growth, by Doxy treatment, prevent rupture, or does the wall continue to weaken and the AAA instead ruptures at a smaller diameter? Using an established animal model of AAA, we begun to determine the changes in tissue mechanics compliance of the aorta as the AAA develops. Our current research is focused on verifying that these changes mimic the observed changes seen in the human population as reported by other researchers, so that we can confidently study how potential drug therapies may affect wall strength and compliance in the human population. The long-term objectives are to understand better factors related to progression of AAA and help verify that drug therapy with Doxy will decrease the chance of rupture by preventing wall weakening and

  19. Experimental study of aortic flow in the ascending aorta via Particle Tracking Velocimetry

    Science.gov (United States)

    Gülan, Utku; Lüthi, Beat; Holzner, Markus; Liberzon, Alex; Tsinober, Arkady; Kinzelbach, Wolfgang

    2012-11-01

    A three-dimensional, pulsatile flow in a realistic phantom of a human ascending aorta with compliant walls is investigated in vitro. Three-Dimensional Particle Tracking Velocimetry (3D-PTV), an image-based, non-intrusive measuring method is used to analyze the aortic flow. The flow velocities and the turbulent fluctuations are determined. The velocity profile at the inlet of the ascending aorta is relatively flat with a skewed profile toward the inner aortic wall in the early systole. In the diastolic phase, a bidirectional flow is observed with a pronounced retrograde flow developing along the inner aortic wall, whereas the antegrade flow migrates toward the outer wall of the aorta. The spatial and temporal evolution of the vorticity field shows that the vortices begin developing along the inner wall during the deceleration phase and attenuate in the diastolic phase. The change in the cross-sectional area is more distinct distal to the inlet cross section. The mean kinetic energy is maximal in the peak systole, whereas the turbulent kinetic energy increases in the deceleration phase and reaches a maximum in the beginning of the diastolic phase. Finally, in a Lagrangian analysis, the temporal evolution of particle dispersion was studied. It shows that the dispersion is higher in the deceleration phase and in the beginning of the diastole, whereas in systole, it is smaller but non-negligible.

  20. A clinical approach to brown adipose tissue in the para-aortic area of the human thorax.

    Science.gov (United States)

    Wei, Huixing; Chiba, Seiichi; Moriwaki, Chinatsu; Kitamura, Hirokazu; Ina, Keisuke; Aosa, Taishi; Tomonari, Kenichiro; Gotoh, Koro; Masaki, Takayuki; Katsuragi, Isao; Noguchi, Hitoshi; Kakuma, Tetsuya; Hamaguchi, Kazuyuki; Shimada, Tatsuo; Fujikura, Yoshihisa; Shibata, Hirotaka

    2015-01-01

    Human thoracic brown adipose tissue (BAT), composed of several subdivisions, is a well-known target organ of many clinical studies; however, the functional contribution of each part of human thoracic BAT remains unknown. The present study analyzed the significance of each part of human thoracic BAT in the association between regional distribution, cellularity, and factors involved in the functional regulation of thoracic BAT. We analyzed 1550 healthy adults who underwent medical check-ups by positron-emission tomography and computed tomography (PET-CT) imaging, 8 cadavers, and 78 autopsy cases in an observational study. We first characterized the difference between the mediastinum and the supraclavicular areas using counts of BAT detection and conditions based on PET-CT outcomes. The measurable important area was then subjected to systematic anatomical and immunohistochemical analyses using anti-uncoupling protein 1 (UCP1) antibody to characterize the cellularity in association with age and sex. In PET-CT scanning, the main site of thoracic BAT was the mediastinum rather than the supraclavicular area (P < 0.05). Systemic macroanatomy revealed that the thumb-sized BAT in the posterior mediastinal descending para-aortic area (paBAT) had feeding vessels from the posterior intercostal arteries and veins and sympathetic/parasympathetic innervation from trunks of the sympathetic and vagus nerves, respectively. Immunohistochemical analysis indicated that the paBAT exhibited immunoreactivity for tyrosine hydroxylase and vesicular acetylcholine transporter located in the pericellular nervous fibers and intracellular UCP1. The brown adipose cells of paBAT showed age-dependent decreases in UCP1 expression (P < 0.05), accompanied by a significant increase in vacuole formation, indicating fat accumulation (P < 0.05), from 10 to 37 years of age (P < 0.01). paBAT may be one of the essential sites for clinical application in BAT study because of its visible anatomy with feeding

  1. Poly(ADP-ribose) polymerase 1 inhibition protects human aortic endothelial cells against LPS-induced inflammation response

    Institute of Scientific and Technical Information of China (English)

    Xiaonu Peng; Wenjun Li; Wei Zhang

    2012-01-01

    Atherosclerosis is a chronic inflammatory disease.Tolllike receptor 4 (TLR4) is an important signaling receptor and plays a critical role in the inflammatory response.Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that can regulate the expression of various inflammatory genes.In this study,we investigated the role and the underlying mechanisms of PARP1 on lipopolysaccharide (LPS)-induced inflammation in human aortic endothelial cells.Compared with the control,LPS stimulation increased the protein expression of TLR4 and PARP1.TLR4 inhibition reduced LPS-induced upregulation of inducible nitric oxide synthase (iNOS) and ICAM-1 as well as PARP1. Nuclear factor κB (NF-κB) inhibition decreased ICAM-1 and iNOS expression.Inhibition of PARP1 decreased protein expression of inflammatory cytokines induced by LPS stimulation,probably through preventing NF-KB nuclear translocation. Our study demonstrated that LPS increased ICAM-1 and iNOS expression via TLR4/PARP1/NF-KB pathway.PARP1 might be an indispensable factor in TLR4-mediated inflammation after LPS stimulation.PARP1 inhibition might shed light on the treatment of LPS-induced inflammatory cytokines expression during atherosclerosis.

  2. Subject-specific estimation of central aortic blood pressure via system identification: preliminary in-human experimental study.

    Science.gov (United States)

    Fazeli, Nima; Kim, Chang-Sei; Rashedi, Mohammad; Chappell, Alyssa; Wang, Shaohua; MacArthur, Roderick; McMurtry, M Sean; Finegan, Barry; Hahn, Jin-Oh

    2014-10-01

    This paper demonstrates preliminary in-human validity of a novel subject-specific approach to estimation of central aortic blood pressure (CABP) from peripheral circulatory waveforms. In this "Individualized Transfer Function" (ITF) approach, CABP is estimated in two steps. First, the circulatory dynamics of the cardiovascular system are determined via model-based system identification, in which an arterial tree model is characterized based on the circulatory waveform signals measured at the body's extremity locations. Second, CABP waveform is estimated by de-convolving peripheral circulatory waveforms from the arterial tree model. The validity of the ITF approach was demonstrated using experimental data collected from 13 cardiac surgery patients. Compared with the invasive peripheral blood pressure (BP) measurements, the ITF approach yielded significant reduction in errors associated with the estimation of CABP, including 1.9-2.6 mmHg (34-42 %) reduction in BP waveform errors (p < 0.05) as well as 5.8-9.1 mmHg (67-76 %) and 6.0-9.7 mmHg (78-85 %) reductions in systolic and pulse pressure (SP and PP) errors (p < 0.05). It also showed modest but significant improvement over the generalized transfer function approach, including 0.1 mmHg (2.6 %) reduction in BP waveform errors as well as 0.7 (20 %) and 5.0 mmHg (75 %) reductions in SP and PP errors (p < 0.05).

  3. Serum Amyloid A Promotes E-Selectin Expression via Toll-Like Receptor 2 in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Eisaku Nishida

    2016-01-01

    Full Text Available Periodontitis is a chronic inflammatory disease that affects the periodontium. Recent studies suggest an association between periodontal and cardiovascular diseases. However, the detailed molecular mechanism is unknown. A previous study has demonstrated that experimental periodontitis induces serum amyloid A (SAA in the liver and peripheral blood of ApoE-deficient mice as an atherosclerosis model. SAA is an acute-phase protein that affects systemic inflammation. The aim of this study is to investigate the atherosclerosis-onset mechanism using human aortic endothelial cells (HAECs stimulated by SAA in vitro. Atherosclerosis PCR array and qPCR analyses showed upregulation of adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in HAECs upon SAA stimulation. In addition, the results demonstrated that Toll-like receptor, TLR2, could serve as an important receptor of SAA in HAECs. Furthermore, small interfering RNA (siRNA against TLR2 inhibited the upregulation of adhesion molecules in HAECs stimulated by SAA. Our results suggest that SAA stimulates the expression of adhesion molecules via TLR2. SAA could be an important molecule for atherosclerosis induced by periodontal disease.

  4. Serum Amyloid A Promotes E-Selectin Expression via Toll-Like Receptor 2 in Human Aortic Endothelial Cells

    Science.gov (United States)

    2016-01-01

    Periodontitis is a chronic inflammatory disease that affects the periodontium. Recent studies suggest an association between periodontal and cardiovascular diseases. However, the detailed molecular mechanism is unknown. A previous study has demonstrated that experimental periodontitis induces serum amyloid A (SAA) in the liver and peripheral blood of ApoE-deficient mice as an atherosclerosis model. SAA is an acute-phase protein that affects systemic inflammation. The aim of this study is to investigate the atherosclerosis-onset mechanism using human aortic endothelial cells (HAECs) stimulated by SAA in vitro. Atherosclerosis PCR array and qPCR analyses showed upregulation of adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in HAECs upon SAA stimulation. In addition, the results demonstrated that Toll-like receptor, TLR2, could serve as an important receptor of SAA in HAECs. Furthermore, small interfering RNA (siRNA) against TLR2 inhibited the upregulation of adhesion molecules in HAECs stimulated by SAA. Our results suggest that SAA stimulates the expression of adhesion molecules via TLR2. SAA could be an important molecule for atherosclerosis induced by periodontal disease. PMID:27799725

  5. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells.

    Science.gov (United States)

    Spigoni, Valentina; Mena, Pedro; Cito, Monia; Fantuzzi, Federica; Bonadonna, Riccardo C; Brighenti, Furio; Dei Cas, Alessandra; Del Rio, Daniele

    2016-08-02

    The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MS(n). The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism.

  6. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Valentina Spigoni

    2016-08-01

    Full Text Available The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS activation in primary human aortic endothelial cells (HAECs. Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MSn. The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism.

  7. Evaluation of regional aortic distensibility using color kinesis.

    Science.gov (United States)

    Kato, Yoshimasa; Kotoh, Keiju; Yamashita, Akio; Furuta, Hidetoshi; Shimazu, Chikasi; Misaki, Takurou

    2003-01-01

    Regional aortic stiffness cannot be evaluated by conventional methods. Regional aortic wall velocity during systole in the descending aorta was evaluated by using transesophageal echocardiography with color kinesis. The authors defined regional aortic distensibility (RAD) by considering pulse pressure, with RAD (microm/s/mm Hg) = (regional aortic wall velocity)/(pulse pressure). RAD was evaluated in 38 patients who had coronary artery disease (CAD) and 10 who did not. RAD decreased depending on aging (partial regression coefficient was -5.39 x 10(-1), pkinesis provides information on characteristic difference between calcified and noncalcified plaque.

  8. Evaluation of Biaxial Mechanical Properties of Aortic Media Based on the Lamellar Microstructure

    Directory of Open Access Journals (Sweden)

    Hadi Taghizadeh

    2015-01-01

    Full Text Available Evaluation of the mechanical properties of arterial wall components is necessary for establishing a precise mechanical model applicable in various physiological and pathological conditions, such as remodeling. In this contribution, a new approach for the evaluation of the mechanical properties of aortic media accounting for the lamellar structure is proposed. We assumed aortic media to be composed of two sets of concentric layers, namely sheets of elastin (Layer I and interstitial layers composed of mostly collagen bundles, fine elastic fibers and smooth muscle cells (Layer II. Biaxial mechanical tests were carried out on human thoracic aortic samples, and histological staining was performed to distinguish wall lamellae for determining the dimensions of the layers. A neo-Hookean strain energy function (SEF for Layer I and a four-parameter exponential SEF for Layer II were allocated. Nonlinear regression was used to find the material parameters of the proposed microstructural model based on experimental data. The non-linear behavior of media layers confirmed the higher contribution of elastic tissue in lower strains and the gradual engagement of collagen fibers. The resulting model determines the nonlinear anisotropic behavior of aortic media through the lamellar microstructure and can be assistive in the study of wall remodeling due to alterations in lamellar structure during pathological conditions and aging.

  9. Aortic root size and prevalence of aortic regurgitation in elite strength trained athletes.

    Science.gov (United States)

    Babaee Bigi, Mohammad Ali; Aslani, Amir

    2007-08-01

    Athletes involved in mainly static or isometric exercise (e.g., weight lifting, power lifting, and bodybuilding) develop pressure overloads due to the high systemic arterial pressure found in this type of exercise. It is hypothesized that chronically elevated aortic wall tension in strength-trained athletes is associated with aortic dilatation and regurgitation. The aim of this study was to evaluate aortic root size and the prevalence of aortic regurgitation in elite strength-trained athletes. The cohort included 100 male athletes (mean age 22.1 +/- 3.6 years; all were finalists or medalists in the country) and 128 healthy age- and height-matched subjects (the control group). Aortic root diameters at end-diastole were measured at 4 locations: (1) the aortic annulus, (2) the sinuses of Valsalva, (3) the sinotubular junction, and (4) the maximal diameter of the proximal ascending aorta. Aortic root diameters at all levels were significantly greater in the strength-trained athletes (p 18 and 36 and 54 months), progressive enlargement was found at all aortic diameters. In conclusion, aortic root diameters in all segments of the aortic root were significantly greater in elite strength-trained athletes compared with an age- and height-matched population.

  10. [Aortic valve replacement as an independent predictive factor for later development of aortic dissection].

    Science.gov (United States)

    von Kodolitsch, Y; Simic, O; Bregenzer, T; Dresler, C; Haverich, A; Nienaber, C A

    1998-08-01

    Dissection of the ascending aorta (type A) following later after aortic valve replacement has been described with increasing frequency. This study analyzes the role of aortic valve replacement for the evolution of late dissection. In a series of 80 consecutive patients with type A dissection, a previous aortic valve replacement had been performed in 12 cases (15%). In addition to arterial hypertension (p syndrome (p factor for type A dissection. Dissection occurred 3 +/- 4 years after aortic valve replacement with a clinical and anatomical profile similar to classic dissection as proven by comparison to a group of 62 patients with classic dissection associated with arterial hypertension or Marfan syndrome. With 75% and 66%, respectively, 30 day and 1 year survival of patients with dissection following later after aortic valve replacement was similar to patients with classic type A dissection. Extensive thinning and/or fragility (p associated with a high risk for late dissection; this finding was substantiated by comparison to a control group of 10 consecutive patients with a similarly dilated aortic root but no dissection. Type and diameter of valve prostheses, cross-clamp time, NYHA functional class, and left ventricular ejection fraction were unrelated to late dissection. Previous aortic valve replacement is an independent predisposing factor for a dissection of the ascending aorta later. At the time of aortic valve replacement, prophylactic replacement or wrapping of the ascending aorta should be considered in patients with a thinned/fragile aortic wall even without a markedly dilated aortic root.

  11. Amendment on the strain measurement of thin-walled human skull shell as intracranial pressure changes

    Institute of Scientific and Technical Information of China (English)

    Xianfang Yue; Li Wang; Feng Zhou

    2008-01-01

    The human skuU,composed of tabula externa,tabula interna,and a porous diploe sandwiched in between,is deformed with changing intracranial pressure (ICP).Because the human skull's thickness is only 6 mm,it is simplified as a thin-walled shell. The objective of this article is to analyze the strain of the thin-walled shell by the stress-strain calculation of a human skull with changing ICP.Under the same loading conditions,using finite element analysis (FEA),the strains of the human skull were calculated and the results were compared with the measurements of the simulative experiment in vitro.It is demonstrated that the strain of the thin-walled shell is totally measured by pasting the one-way strain foils on the exterior surface of the shell with suitable amendment for data.The amendment scope of the measured strain values of the thin-walled shell is from 13.04% to 22.22%.

  12. Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Hung-hsing CHAO; Ju-chi LIU; Jia-wei LIN; Cheng-hsien CHEN; Chieh-hsi WU; Tzu-hurng CHENG

    2008-01-01

    Aim: Recent experimental and human studies have shown that hyperuricemia is associated with hypertension and cardiovascular diseases. Elevated levels of endotheliu-1 (ET-1) has been regarded as one of the most powerful indepen-dent predictors of cardiovascular diseases. For investigating whether uric acidinduced vascular diseases are related to ET-1, the uric acid-induced ET-1 expression in human aortic smooth muscle cells (HASMC) was examined. Methods: Cultured HASMC treated with uric acid, cell proliferation and ET-1 expression were examined. Antioxidant pretreatments on uric acid-induced extracellular signal-regulated kinases (ERK) phosphorylation were carried out to elucidate the redox-sensitive pathway in proliferation and ET-1 gene expression. Results: Uric acid was found to increase HASMC proliferation, ET-1 expression and reactive oxygen species production. The ability of both N-acetylcysteine and apocynin (1-[4-hydroxy-3-methoxyphenyl]ethanone, a NADPH oxidase inhibitor) to inhibit uric acid-induced ET-1 secretion and cell proliferation suggested the involvement of intracellular redox pathways. Furthermore, apocynin, and p47phox small interfering RNA knockdown inhibited ET-1 secretion and cell proliferation induced by uric acid. Inhibition of ERK by U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene) significantly suppressed uric acid-induced ET-I expression, implicating this pathway in the response to uric acid. In addition, uric acid increased the transcription factor activator protein-1 (AP-1) medi-ated reporter activity, as well as the ERK phosphorylation. Mutational analysis of the ET-1 gene promoter showed that the AP-1 binding site was an important cis-element in uric acid-induced ET-1 gene expression. Conclusion: This is the first observation of ET-1 regulation by uric acid in HASMC, which implicates the important role of uric acid in the vascular changes associated with hypertension and vascular diseases.

  13. Staphylococcal β-Toxin Modulates Human Aortic Endothelial Cell and Platelet Function through Sphingomyelinase and Biofilm Ligase Activities

    Science.gov (United States)

    Herrera, Alfa; Kulhankova, Katarina; Sonkar, Vijay K.; Dayal, Sanjana; Klingelhutz, Aloysius J.; Salgado-Pabón, Wilmara

    2017-01-01

    ABSTRACT Staphylococcus aureus causes many infections, such as skin and soft tissue, pneumonia, osteomyelitis, and infective endocarditis (IE). IE is an endovascular infection of native and prosthetic valves and the lining of the heart; it is characterized by the formation of cauliflower-like “vegetations” composed of fibrin, platelets, other host factors, bacteria, and bacterial products. β-Toxin is an S. aureus virulence factor that contributes to the microorganism’s ability to cause IE. This cytolysin has two enzymatic activities: sphingomyelinase (SMase) and biofilm ligase. Although both activities have functions in a rabbit model of IE, the mechanism(s) by which β-toxin directly affects human cells and is involved in the infectious process has not been elucidated. Here, we compared the in vitro effects of purified recombinant wild-type β-toxin, SMase-deficient β-toxin (H289N), and biofilm ligase-deficient β-toxin (H162A and/or D163A) on human aortic endothelial cells (HAECs) and platelets. β-Toxin was cytotoxic to HAECs and inhibited the production of interleukin 8 (IL-8) from these cells by both SMase and biofilm ligase activities. β-Toxin altered HAEC surface expression of CD40 and vascular cell adhesion molecule 1 (VCAM-1). HAECs treated with β-toxin displayed granular membrane morphology not seen in treatment with the SMase-deficient mutant. The altered morphology resulted in two possibly separable activities, cell rounding and redistribution of cell membranes into granules, which were not the result of endosome production from the Golgi apparatus or lysosomes. β-Toxin directly aggregated rabbit platelets via SMase activity. PMID:28325766

  14. From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

    Science.gov (United States)

    Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

    2014-07-03

    Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

  15. Triptans induce vasoconstriction of human arteries and veins from the thoracic wall

    DEFF Research Database (Denmark)

    Wackenfors, Angelica; Jarvius, Malin; Ingemansson, Richard;

    2005-01-01

    A common side effect of migraine treatment with triptans is chest symptoms. The origin of these symptoms is not known. The aim of the present study was to examine the vasocontractile effect of triptans in human arteries and veins from the thoracic wall and in coronary artery bypass grafts. In vitro...... detected by real-time PCR in all blood vessels studied. In conclusion, triptans induce vasoconstriction in arteries and veins from the thoracic wall, most likely by activation of 5-HT1B receptors. This response could be observed in only 38% to 57% of the patients, which may provide an explanation for why...

  16. Bicuspid Aortic Valve

    Science.gov (United States)

    2006-08-01

    aortic valvular disease, endocarditis, ascending aortic aneurysm and aortic dissection.1-4 There is also an association of BAV with coarctation of...for aortic aneurysm , patients with BAV appear to have additional risks for aortic disease. Nistri et al.12 reported significant aortic root...Congenital heart disease in patients with Turner’s syndrome. Italian study group for Turner syndrome (ISGTS). J Pediatr 1998; 133:688-692. 7. Schmid

  17. Aortic Stenosis.

    Science.gov (United States)

    Bakaeen, Faisal G; Rosengart, Todd K; Carabello, Blase A

    2017-01-03

    This issue provides a clinical overview of aortic stenosis, focusing on screening, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  18. [Morphometric characteristics of human colon wall as anatomic basis for microsurgical anastomoses].

    Science.gov (United States)

    Konovalov, D Iu

    2007-01-01

    This article describes the morphometric characteristics and some peculiarities of microsurgical anatomy of human colon wall. The thickness of colon wall varied from 495 to 3501 microm in the areas between teniae and from 1103 to 4007 microm in the areas of teniae, the average values were equal to 1693+93.3 and 2602+85 microm, respectively. The width of teniae was 3.5-10.3 mm (6.2+0.3 mm on the average). The thickness of tunica muscularis along the colon prevailed over the thickness of other tunics and increased caudally, while the thickness of submucosa diminished. Marked variability and small thickness of both the colon wall and its layers, differences of these characteristics in the areas of teniae musculares and between them support the expediency of the application of microsurgical operative technique in the operations performed on the colon.

  19. Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway.

    Science.gov (United States)

    Wang, Chunmao; Chang, Qian; Qian, Xiangyang; Tian, Chuan; Sun, Xiaogang

    2015-07-01

    The cellular and molecular mechanisms responsible for human idiopathic ascending aortic aneurysm (IAAA) remain unknown. Matrix metalloproteinase-2 (MMP-2) is a key enzyme for the degradation of extracellular matrix in aneurysmal walls. The aim of this study was to elucidate the role of the angiotensin II (Ang II) pathway in MMP-2 induction in IAAA aortic walls. Quantitative polymerase chain reaction and western blot analysis were used to compare the MMP-2 mRNA and protein levels in ascending aortic specimens with those in IAAA patients (n = 10) and heart transplant donors (n = 5) without any aortopathy. It was found that MMP-2 expression was significantly increased, which was associated with elastic lamellae disruption in IAAA walls. Additionally, the expression levels of angiotensinogen (AGT) and Ang II in the ascending aortic tissues from individuals with and without IAAAs were detected by western blot analysis and radioimmunoassay, respectively. The results demonstrated that the expressions of AGT and Ang II protein were significantly increased in the ascending aortic tissues of IAAA patients. Furthermore, whether Ang II induces MMP-2 expression was investigated using human IAAA walls ex vivo culture. It was found that exogenous Ang II increased the MMP-2 expression in a dose-dependent manner, which was completely inhibited by the Ang II type 1 receptor (AT1R) inhibitor candesartan and was mediated by c-Jun N-terminal kinase (JNK) activation. Taken together, these results indicate that Ang II can induce an increase of MMP-2 expression via AT1R and JNK in ex vivo cultured IAAA aortic walls, and suggest that angiotensin receptor blocker (ARB) drugs and JNK inhibitors have the potential in the prevention or treatment of IAAAs.

  20. Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells

    Science.gov (United States)

    Weikel, Karen A.; Cacicedo, José M.; Ruderman, Neil B.; Ido, Yasuo

    2016-01-01

    High concentrations of glucose and palmitate increase endothelial cell inflammation and apoptosis, events that often precede atherogenesis. They may do so by decreasing basal autophagy and AMP-activated protein kinase (AMPK) activity, although the mechanisms by which this occurs are not clear. Decreased function of the lysosome, an organelle required for autophagy and AMPK, have been associated with hyperactivity of glycogen synthase kinase 3β (GSK3β). To determine whether GSK3β affects nutrient-induced changes in autophagy and AMPK activity, we used a primary human aortic endothelial cell (HAEC) model of type 2 diabetes that we had previously characterized with impaired AMPK activity and autophagy [Weikel et al. (2015) Am. J. Phys. Cell Physiol. 308, C249–C263]. Presently, we found that incubation of HAECs with excess nutrients (25 mM glucose and 0.4 mM palmitate) increased GSK3β activity and impaired lysosome acidification. Suppression of GSK3β in these cells by treatment with a chemical inhibitor or overexpression of kinase-dead GSK3β attenuated these lysosomal changes. Under control and excess nutrient conditions, knockdown of GSK3β increased autophagosome formation, forkhead box protein O1 (FOXO1) activity and AMPK signalling and decreased Akt signalling. Similar changes in autophagy, AMPK and Akt signalling were observed in aortas from mice treated with the GSK3β inhibitor CHIR 99021. Thus, increasing basal autophagy and AMPK activity by inhibiting GSK3β may be an effective strategy in the setting of hyperglycaemia and dyslipidaemia for restoring endothelial cell health and reducing atherogenesis. PMID:27534430

  1. 2-Methoxycinnamaldehyde inhibits the TNF-α-induced proliferation and migration of human aortic smooth muscle cells.

    Science.gov (United States)

    Jin, Young-Hee; Kim, Soo-A

    2017-01-01

    The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a crucial event in the development of atherosclerosis, and tumor necrosis factor-α (TNF-α) is actively involved in this process by enhancing the proliferation and migration of VSMCs. 2-Methoxycinnamaldehyde (MCA) is a natural compound of Cinnamomum cassia. Although 2-hydroxycinnamaldehyde (HCA), another compound from Cinnamomum cassia, has been widely studied with regard to its antitumor activity, MCA has not attracted researchers' interest due to its mild toxic effects on cancer cells and its mechanisms of action remain unknown. In this study, we examined the effects of MCA on the TNF-α-induced proliferation and migration of human aortic smooth muscle cells (HASMCs). As shown by our results, MCA inhibited TNF-α-induced cell proliferation by reducing the levels of cyclin D1, cyclin D3, CDK4 and CDK6, and increasing the levels of the cyclin-dependent kinase inhibitors, p21 and p27, without resulting in cellular cytotoxicity. Furthermore, MCA decreased the level of secreted matrix metalloproteinase (MMP)-9 by inhibiting MMP-9 transcription. Unexpectedly, MCA did not affect the TNF-α-induced levels of mitogen-activated protein kinases (MAPKs). However, by showing that MCA potently inhibited the degradation of IκBα and the subsequent nuclear translocation of nuclear factor-κB (NF-κB), we demonstrated that MCA exerts its effects through the NF-κB signaling pathway. MCA also effectively inhibited platelet-derived growth factor (PDGF)-induced HASMC migration. Taken together, these observations suggest that MCA has the potential for use as an anti-atherosclerotic agent.

  2. Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jian tao Song

    Full Text Available OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21 is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs. METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb. FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4 participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.

  3. Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans.

    Science.gov (United States)

    Bernelot Moens, Sophie J; Verweij, Simone L; Schnitzler, Johan G; Stiekema, Lotte C A; Bos, Merijn; Langsted, Anne; Kuijk, Carlijn; Bekkering, Siroon; Voermans, Carlijn; Verberne, Hein J; Nordestgaard, Børge G; Stroes, Erik S G; Kroon, Jeffrey

    2017-05-01

    Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). Arterial wall inflammation and bone marrow activity were measured using (18)F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of (18)F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07-5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27-0.40]; Pcholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD. © 2017 American Heart Association, Inc.

  4. From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Martinez-Pinna, Roxanna; Lindholt, Jes Sanddal; Madrigal-Matute, Julio

    2014-01-01

    Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood...... cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC......) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels...

  5. Micromanaging Abdominal Aortic Aneurysms

    Directory of Open Access Journals (Sweden)

    Lars Maegdefessel

    2013-07-01

    Full Text Available The contribution of abdominal aortic aneurysm (AAA disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to “fine tune” the translational output of their target messenger RNAs (mRNAs by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility.

  6. Simulation and signal processing of through wall UWB radar for human being's periodic motions detection

    Science.gov (United States)

    Li, Jing; Liu, Fengshan; Xu, Penglong; Zeng, Zhaofa

    2013-05-01

    The human's Micro-Doppler signatures resulting from breathing, arm, foot and other periodic motion can provide valuable information about the structure of the moving parts and may be used for identification and classification purposes. In this paper, we carry out simulate with FDTD method and through wall experiment with UWB radar for human being's periodic motion detection. In addition, Advancements signal processing methods are presented to classify and to extract the human's periodic motion characteristic information, such as Micro-Doppler shift and motion frequency. Firstly, we apply the Principal Component Analysis (PCA) with singular value decomposition (SVD) to denoise and extract the human motion signal. Then, we present the results base on the Hilbert-Huang transform (HHT) and the S transform to classify and to identify the human's micro-Doppler shift characteristics. The results demonstrate that the combination of UWB radar and various processing methods has potential to detect human's Doppler signatures effectively.

  7. Analysis of Human's Motions Based on Local Mean Decomposition in Through-wall Radar Detection

    Science.gov (United States)

    Lu, Qi; Liu, Cai; Zeng, Zhaofa; Li, Jing; Zhang, Xuebing

    2016-04-01

    Observation of human motions through a wall is an important issue in security applications and search-and rescue. Radar has advantages in looking through walls where other sensors give low performance or cannot be used at all. Ultrawideband (UWB) radar has high spatial resolution as a result of employment of ultranarrow pulses. It has abilities to distinguish the closely positioned targets and provide time-lapse information of targets. Moreover, the UWB radar shows good performance in wall penetration when the inherently short pulses spread their energy over a broad frequency range. Human's motions show periodic features including respiration, swing arms and legs, fluctuations of the torso. Detection of human targets is based on the fact that there is always periodic motion due to breathing or other body movements like walking. The radar can gain the reflections from each human body parts and add the reflections at each time sample. The periodic movements will cause micro-Doppler modulation in the reflected radar signals. Time-frequency analysis methods are consider as the effective tools to analysis and extract micro-Doppler effects caused by the periodic movements in the reflected radar signal, such as short-time Fourier transform (STFT), wavelet transform (WT), and Hilbert-Huang transform (HHT).The local mean decomposition (LMD), initially developed by Smith (2005), is to decomposed amplitude and frequency modulated signals into a small set of product functions (PFs), each of which is the product of an envelope signal and a frequency modulated signal from which a time-vary instantaneous phase and instantaneous frequency can be derived. As bypassing the Hilbert transform, the LMD has no demodulation error coming from window effect and involves no negative frequency without physical sense. Also, the instantaneous attributes obtained by LMD are more stable and precise than those obtained by the empirical mode decomposition (EMD) because LMD uses smoothed local

  8. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate...... the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation) of ERK1/2 as a functional signal molecule for endothelin receptor activity. RESULTS: Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 microM). The activation of ERK1/2...... was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2...

  9. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Edvinsson Lars

    2009-07-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 is a potent vasoactive peptide, which induces vasoconstriction and proliferation in vascular smooth muscle cells (VSMCs through activation of endothelin type A (ETA and type B (ETB receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2 mitogen-activated protein kinases (MAPK are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation of ERK1/2 as a functional signal molecule for endothelin receptor activity. Results Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 μM. The activation of ERK1/2 was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2 was completely abolished by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1 inhibitor PD98059. A dual endothelin receptor antagonist bosentan or the ETA antagonist BQ123 blocked the ET-1 effect, while the ETB antagonist BQ788 had no significant effect. However, a selective ETB receptor agonist, Sarafotoxin 6c (S6c caused a time-dependent ERK1/2 activation with a maximal effect by less than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan concentration up to 10 μM further inhibited ET-1-induced activation of ERK1/2 and had a stronger inhibitory effect than BQ123 or the combined use of BQ123 and BQ788. To further explore ET-1 intracellular signaling, PKC inhibitors (staurosporin and GF109203X, PKC-delta inhibitor (rottlerin, PKA inhibitor (H-89, and phosphatidylinositol 3-kinase (PI3K inhibitor (wortmannin were applied. The inhibitors showed significant inhibitory effects on ET-1

  10. Thoracic Aortic Rupture and Aortopulmonary Fistulation in the Friesian Horse : Histomorphologic Characterization

    NARCIS (Netherlands)

    Ploeg, M; Saey, V; Delesalle, C; Gröne, A; Ducatelle, R; de Bruijn, M; Back, W; van Weeren, P R; van Loon, G; Chiers, K

    Aortic rupture in horses is a rare condition. Although it is relatively common in the Friesian breed, only limited histopathologic information is available. Twenty Friesian horses (1-10 years old) were diagnosed with aortic rupture by postmortem examination. Ruptured aortic walls were analyzed with

  11. Toxicology Study of Single-walled Carbon Nanotubes and Reduced Graphene Oxide in Human Sperm

    OpenAIRE

    2016-01-01

    Carbon-based nanomaterials such as single-walled carbon nanotubes and reduced graphene oxide are currently being evaluated for biomedical applications including in vivo drug delivery and tumor imaging. Several reports have studied the toxicity of carbon nanomaterials, but their effects on human male reproduction have not been fully examined. Additionally, it is not clear whether the nanomaterial exposure has any effect on sperm sorting procedures used in clinical settings. Here, we show that ...

  12. Aortic valve bypass

    DEFF Research Database (Denmark)

    Lund, Jens T; Jensen, Maiken Brit; Arendrup, Henrik

    2013-01-01

    In aortic valve bypass (AVB) a valve-containing conduit is connecting the apex of the left ventricle to the descending aorta. Candidates are patients with symptomatic aortic valve stenosis rejected for conventional aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI...

  13. Quadricuspid Aortic Valve

    Directory of Open Access Journals (Sweden)

    Mehmet Taşar

    2013-03-01

    Full Text Available Quadricuspid aortic valve is an extremely rare congenital defect. Isolated form appears frequently. It is seen with aortic valve regurgitation in adulthood. This case report presents a rare clinical finding of an isolated quadricuspid aortic valve with aortic regurgitation in an 64-year-old female who was referred for cardiac evaluation due to newly identified murmur.

  14. Pathogenesis of solitary right aortic arch: a mass effect hypothesis based on observations of serial human embryonic sections.

    Science.gov (United States)

    Jin, Zhe W; Yamada, Tomonori; Kim, Ji H; Rodríguez-Vázquez, José F; Murakami, Gen; Arakawa, Keiji

    2017-03-01

    In general, solitary right aortic arch carries the left-sided ductus arteriosus communicating between the left subclavian and pulmonary arteries or the right-sided ductus connecting the descending aorta to the left pulmonary artery. Serial sections of fifteen 5- to 6-week-old embryos and ten 8- to 9-week-old fetuses suggested that the pathogenesis was unrelated to inversion due to dysfunction in gene cascades that control the systemic left/right axis. With inversion, conversely, the ductus or the sixth pharyngeal arch artery should connect to the right pulmonary artery. The disappearance of the right aortic arch started before the caudal migration of the aortic attachment of the ductus. Sympathetic nerve ganglia developed immediately posterior to both aortae, with a single embryonic specimen showing a large ganglion at the midline close to the union of the aortic arches. These ganglia may interfere with blood flow through the distal left arch, resulting in the ductus ending at the descending aorta behind the oesophagus. In another fetus examined, a midline shift of the ductus course resulted in the trachea curving posteriorly. Therefore, solitary right arch is likely to accompany abnormalities of the surrounding structures. The timing and site of the obstruction should be different between types: an almost midline obstruction near the aortic union needed for the development of the left-sided ductus and a distal obstruction near the left subclavian arterial origin needed for the development of the right-sided ductus. A mass effect of the sympathetic ganglia may explain the pathogenesis of any type of anomalous ductus arteriosus shown in previous reports of the solitary right arch.

  15. MCP-1 Stimulates MMP-9 Expression via ERK 1/2 and p38 MAPK Signaling Pathways in Human Aortic Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Ci-Qiu Yang

    2014-07-01

    Full Text Available Objective: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1 in the formation and development of human abdominal aortic aneurysm (AAA. Methods: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs with human recombinant MCP-1. Results: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9 expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs extracellular signal regulated kinase (ERK, c-Jun amino terminal kinase (JNK1/2 and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway and SB203580 (inhibitor of the p38 MAPK pathway, but not SP600125 (inhibitor of the JNK1/2 pathway. Conclusion: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.

  16. Silencing of Bcl-2 gene expression by siRNA transfection inhibits the protective effect of fluvastatin against cell apoptosis in human aortic endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Wenwen Zhong; Yang Liu; Jian Li; Hui Tian

    2008-01-01

    Objective To study the protective effect of fluvastatin,one of the HMG-CoA reductase inhibitors (statins),against oxygen radical-induced oxidative damages in human aortic endothelial cell,and the role of Bcl-2 in this protection.Methods Human aortic endothelial cells with or without Bcl-2 siRNA transfection were subjected to 1-100 nM of fluvastatin and 100 la hydrogen peroxide for 24 hours.Bcl-2 mRNA and protein expression were measured by Taqman quantitative PCR and Western blotting.Cell apoptosis was measured by normal and fluorescent microscopy and Cell Death Detection ELISA.Results In the Bcl-2-expressed cells,fluvastatin significantly reversed hydrogen peroxide-induced microscopic apoptosis and apoptotic DNA fragmentation,which were accompanied by a markedly upregulation of Bcl-2 expression by fluvastatin.However,the endothelial protection by fluvastatin was completely lost in Bcl-2 siRNA transfected cells.Conclusion Fluvastatin protects human endothelial cells against oxygen radical-induced cell apoptosis in vitro,and this protection seemed to be mediated in a Bcl-2 dependent pathway.(J Geriatr Cardil 12008;5:33-38)

  17. Hesr2 knockout mice develop aortic valve disease with advancing age.

    Science.gov (United States)

    Kokubo, Hiroki; Miyagawa-Tomita, Sachiko; Nakashima, Yasumi; Kume, Tsutomu; Yoshizumi, Masao; Nakanishi, Toshio; Saga, Yumiko

    2013-03-01

    Acquired heart diseases, such as valve disease, are major causes of human morbidity and mortality. However, the pathological mechanisms underlying these diseases are largely unknown. Our aim is to identify the role of the hairy and enhancer of split-related (Hesr)-2 gene in the adult heart. Echocardiography detected heart dysfunctions indicative of aortic valve anomalies, stenosis, and regurgitation, in ≈59% of >12-month-old Hesr2 knockout survivor mice. Morphological and histological analyses revealed thickened semilunar valves with increased fibrotic areas, indicating that sclerotic degeneration of valves is the main cause of aortic valve disease. The expression of osteogenic genes, such as osteopontin and sclerostin, were upregulated in the mutants, and the overexpression of sclerostin in endothelial cells resulted in thickened semilunar valves with increased fibrotic areas, similar to that seen in the Hesr2 knockout mice, suggesting that Hesr2 can regulate osteogenic gene expression in valves. Reduced left ventricular function, which may be caused by increased ventricular interstitial fibrosis, and enlarged myocardial cell size without ventricular wall thickening were found in both aortic valve stenosis/regurgitation-positive (33%) and aortic valve stenosis/regurgitation-negative (38%) subpopulations in 12-month-old survivor mice. Dilated left ventricular internal dimensions were specifically detected in the aortic valve stenosis/regurgitation-positive subpopulation, thus suggesting that the degeneration of cardiomyocytes is influenced by irregular hemodynamics. These data revealed that survivor mice lacking the Hesr2 gene exhibit fibrosis in the aortic valve and ventricle in adulthood, thus suggesting that Hesr2 plays an important role in maintaining the homeostasis of the aortic valve and ventricle.

  18. Through-wall imaging and characterization of human activity using ultrawideband (UWB) random noise radar

    Science.gov (United States)

    Lai, Chieh-Ping; Narayanan, Ram M.

    2005-05-01

    Recent terrorist activities and law-enforcement situations involving hostage situations underscore the need for effective through-wall imaging. Current building interior imaging systems are based on short-pulse waveforms, which require specially designed antennas to subdue unwanted ringing. In addition, periodically transmitted pulses of energy are easily recognizable by the intelligent adversary who may employ appropriate countermeasures to confound detection. A coherent polarimetric random noise radar architecture is being developed based on UWB technology and software defined radio, which has great promise in its ability to covertly image obscured targets. The main advantages of the random noise radar lie in two aspects: first, random noise waveform has an ideal "thumbtack" ambiguity function, i.e., its down range and cross range resolution can be separately controlled, thus providing unambiguous high resolution imaging at any distance; second, random noise waveform is inherently low probability of intercept (LPI) and low probability of detection (LPD), i.e., it is immune from detection, jamming, and interference. Thus, it is an ideal candidate sensor for covert imaging of obscured regions in hostile environments. The coherency in the system can be exploited to field a fully-polarimetric system that can take advantage of polarization features in target recognition. Moving personnel can also be detected using Doppler processing. Simulation studies are used to analyze backscattered signals from the walls, and humans and other targets behind the walls. Real-time data processing shows human activity behind the wall and human target tracking. The high resolution provides excellent multipath and clutter rejection.

  19. Gender differences in abdominal aortic aneurysms.

    Science.gov (United States)

    Hannawa, Kevin K; Eliason, Jonathan L; Upchurch, Gilbert R

    2009-01-01

    Abdominal aortic aneurysms (AAAs) comprise the tenth leading cause of death in Caucasian males 65 to 74 years of age and accounted for nearly 16,000 deaths overall in 2000. Therefore, understanding the pathophysiology of AAAs is an important undertaking. Clinically, multiple risk factors are associated with the development of AAAs, including increasing age, positive smoking history, and hypertension. Male gender is also a well-established risk factor for the development of an AAA, with a 4:1 male to female ratio. The reason for this gender disparity is unknown. The pathogenesis of AAAs formation is complex and multifactorial. Histologically, AAAs are characterized by early chemokine-driven leukocyte infiltration into the aortic wall. Subsequent destruction of elastin and collagen in the media and adventitia ensues owing to excessive local production of matrix-degrading enzymes and is accompanied by smooth muscle cell loss and thinning of the aortic wall. At present, no medical therapies are available to treat patients with aortic aneurysms, using only the crude measurement of aortic diameter as a threshold for which patients must undergo life-threatening and costly surgery. Defining the early mechanisms underlying gender-related differences in AAA formation is critical as understanding differences in disease patterns based on gender may allow us to develop new translational approaches to the prevention and treatment of patients with aortic aneurysms.

  20. Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2.

    Science.gov (United States)

    Wang, Chunmao; Qian, Xiangyang; Sun, Xiaogang; Chang, Qian

    2015-12-01

    Increased levels of angiotensin II (Ang II) and activated matrix metalloproteinase 2 (MMP-2) produced by human aortic smooth muscle cells (human ASMCs) have recently been implicated in the pathogenesis of thoracic aortic aneurysm (TAA). Additionally, angiotensin II type 1 receptor (AT1R)-mediated extracellular signal-regulated kinase (ERK)1/2 activation contributes to TAA development in Marfan Syndrome. However, there is scant data regarding the relationship between Ang II and MMP-2 expression in human ASMCs. Therefore, we investigated the effect of Ang II on MMP-2 expression in human ASMCs and used Western blotting to identify the Ang II receptors and intracellular signaling pathways involved. Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence data demonstrated that Ang II receptors were expressed on human ASMCs. Additionally, Ang II increased the expression of Ang II type 2 receptor (AT2R) but not AT1R at both the transcriptional and translational levels. Furthermore, Western blotting showed that Ang II increased MMP-2 expression in human ASMCs in a dose- and time-dependent manner. This response was completely inhibited by the AT1R inhibitor candesartan but not by the AT2R blocker PD123319. In addition, Ang II-induced upregulation of MMP-2 was mediated by the activation of ERK1/2, whereas p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) had no effect on this process. In conclusion, these results indicate that Ang II can increase the expression of MMP-2 via AT1 receptor and ERK1/2 signaling pathways in human ASMCs and suggest that antagonists of AT1R and ERK1/2 may be useful for treating TAAs.

  1. Human cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a humanized mouse aortic xenograft model.

    Science.gov (United States)

    Abele-Ohl, S; Leis, M; Wollin, M; Mahmoudian, S; Hoffmann, J; Müller, R; Heim, C; Spriewald, B M; Weyand, M; Stamminger, T; Ensminger, S M

    2012-07-01

    Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu-PBL)/Rag-2(-/-) γc(-/-) mouse-xenograft-model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue-typed and infected with HCMV. Then, size-matched sidebranches were implanted into the infrarenal aorta of Rag-2(-/-) γc(-/-) mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV-infection was confirmed by Taqman-PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC-reconstituted Rag-2(-/-) γc(-/-) animals showed splenic chimerism levels ranging from 1-16% human cells. After reconstitution, Rag-2(-/-) γc(-/-) mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM-1 and PDGF-R-β expression after HCMV-infection of the graft. Arterial grafts from unreconstituted Rag-2(-/-) γc(-/-) recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV-infection as an isolated risk factor and the development of transplant-arteriosclerosis in a humanized mouse arterial-transplant-model possibly by elevated ICAM-1 and PDGF-R-β expression.

  2. The effects of low density lipoproteins modified by incubation with chondroitin 6-sulfate on human aortic smooth muscle cells.

    Science.gov (United States)

    Tîrziu, D; Jinga, V V; Serban, G; Simionescu, M

    1999-11-01

    One of the first changes that take place within the artery intima at the inception of atherosclerosis is the accumulation of LDL-derived modified lipoproteins which appear as subendothelial lipid droplets and vesicles. With time, the LDL retention and interaction with intimal chondroitin sulfate-proteoglycans may induce further structural and functional modification of the lipoproteins. The aim of this study was to produce 'in vitro' modified lipoproteins by LDL incubation with chondroitin 6-sulfate (CS, at 37 degrees C, for 48 h, in the absence of antioxidants) and to test their effects on cultured human aortic smooth muscle cells (SMCs). CS induced LDL modification (CS-mLDL) consisted in formation of a mixture of fused particles (up to 150 nm diameter) and monomers with a small content of lipid peroxides and a partially degraded apo B-100, corresponding to a mild oxidation. Upon incubation with SMCs, CS-mLDL produced a concentration-dependent stimulation of 3H-thymidine incorporation, that, at low concentration (25 microg/ml), was 2-3-fold higher than that obtained when native LDL was used; this increase correlates well with the level of CS-mLDL uptake at the same concentration. Besides the mitogenic effect, CS-mLDL induced a significant stimulation of SMCs migration, comparable with that reported for oxidized LDL. Upon incubation with CS-mLDL, SMCs accumulated lipid droplets of various number and dimension, as revealed by Nile red staining and electron microscopy. Competition studies performed in the presence of 20-fold excess of native LDL and acetyl LDL showed that 125I-CS-mLDL were taken up both by LDL receptor and scavenger receptor. At high concentration (200 microg/ml), CS-mLDL had a cytotoxic effect that was not significantly different from that of native LDL. Together these results provide evidence of (i) the direct alteration produced by CS on LDL and (ii) the effect of CS-mLDL on SMCs migration, proliferation and transformation in lipid-laden cells

  3. A mechanistic model on the role of "radially-running" collagen fibers on dissection properties of human ascending thoracic aorta.

    Science.gov (United States)

    Pal, Siladitya; Tsamis, Alkiviadis; Pasta, Salvatore; D'Amore, Antonio; Gleason, Thomas G; Vorp, David A; Maiti, Spandan

    2014-03-21

    Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovascular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber micro-architecture, obtained in a parallel study from multi-photon microscopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence.

  4. miR-503 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting the insulin receptor.

    Science.gov (United States)

    Bi, Rui; Ding, Fangbao; He, Yi; Jiang, Lianyong; Jiang, Zhaolei; Mei, Ju; Liu, Hao

    2016-12-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) is a common feature of disease progression in atherosclerosis. Here, we investigated the potential role of miR-503 in platelet-derived growth factor (PDGF)-induced proliferation and migration of human aortic smooth muscle cells and the underlying mechanisms of action. miR-503 expression was significantly downregulated in a dose- and time-dependent manner following PDGF treatment. Introduction of miR-503 mimics into cultured SMCs significantly attenuated cell proliferation and migration induced by PDGF. Bioinformatics analyses revealed that the insulin receptor (INSR) is a target candidate of miR-503. miR-503 suppressed luciferase activity driven by a vector containing the 3'-untranslated region of INSR in a sequence-specific manner. Downregulation of INSR appeared critical for miR-503-mediated inhibitory effects on PDGF-induced cell proliferation and migration in human aortic SMCs. Based on the collective data, we suggest a novel role of miR-503 as a regulator of VSMC proliferation and migration through modulating INSR.

  5. Possible dual role of decorin in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Koshiro Ueda

    Full Text Available Abdominal aortic aneurysm (AAA is characterized by chronic inflammation, which leads to pathological remodeling of the extracellular matrix. Decorin, a small leucine-rich repeat proteoglycan, has been suggested to regulate inflammation and stabilize the extracellular matrix. Therefore, the present study investigated the role of decorin in the pathogenesis of AAA. Decorin was localized in the aortic adventitia under normal conditions in both mice and humans. AAA was induced in mice using CaCl2 treatment. Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers. Local administration of exogenous decorin prevented the development of CaCl2-induced AAA. However, decorin was highly expressed in the degenerative lesions of human AAA walls, and this expression positively correlated with matrix metalloproteinase (MMP-9 expression. In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages. The results suggest that decorin plays a dual role in AAA. Adventitial decorin in normal aorta may protect against the development of AAA, but macrophages expressing decorin in AAA walls may facilitate the progression of AAA by up-regulating MMP-9 secretion.

  6. Regional calcium distribution and ultrasound images of the vessel wall in human carotid arteries

    Science.gov (United States)

    Szikszai, Z.; Kertész, Zs.; Uzonyi, I.; Szíki, G. Á.; Magyar, M. T.; Molnár, S.; Ida, Y.; Csiba, L.

    2005-04-01

    Arterial calcification can take place at two sites in the vessel wall: the intima and the media. Intimal calcification occurs exclusively within atherosclerotic plaques, while medial calcification may develop independently. Extensive calcified plaques in the carotid arteries can be easily detected by B-mode ultrasonic imaging. The calcium content might correlate with the ultrasound reflectance of the vessel wall, and could be a surrogate marker for arteriosclerosis. In this study, segments of human carotid arteries collected at autopsy were examined by ultrasonography in vitro and calcium distributional maps of sections from the same segments were determined by particle induced X-ray emission. Our aim was to make a first step towards investigating the relationship between the calcium distributional maps and the respective ultrasound images.

  7. Upregulation of HMGB1 in wall of ruptured and unruptured human cerebral aneurysms: preliminary results.

    Science.gov (United States)

    Zhang, Dingding; Wu, Wei; Yan, Huiying; Jiang, Tianwei; Liu, Ming; Yu, Zhuang; Li, Hua; Hang, Chunhua

    2016-02-01

    A growing body of evidence suggests that inflammation plays a crucial role in cerebral aneurysm initiation, progression, and rupture. High-mobility group box 1 (HMGB1) is a non-histone nuclear protein that can serve as an alarmin to drive the pathogenesis of inflammatory disease. The purpose of this study was to investigate the expression of HMGB1 in the wall of ruptured and unruptured human cerebral aneurysms. Human cerebral aneurysms (25 ruptured and 16 unruptured) were immunohistochemically stained for HMGB1. As controls, four specimens of the middle cerebral arteries obtained at autopsy were also immunostained. Immunofluorescence double staining was used to determine HMGB1 cellular distribution. HMGB1 was nearly undetectable in the controls. All aneurysm tissues stained positive for HMGB1 monoclonal antibody, and expression of HMGB1 was more abundant in ruptured aneurysm tissue than unruptured aneurysms (p < 0.05). Furthermore, the expression of HMGB1 had no correlation with aneurysm size and time resected after the rupture. HMGB1 nuclear immunoreactivity was co-localized with immunoreactivity of CD3 in T lymphocytes, CD20 in B lymphocytes, CD68 in macrophages, α-SMA in smooth muscle cells, and CD31 in endothelial cells. Cytoplasmic HMGB1 localization was also detected in macrophages and T lymphocytes. Taken together, HMGB1 is expressed in the wall of human cerebral aneurysms and is more abundant in ruptured aneurysms than in unruptured ones. These data indicate a possible role of HMGB1 in the pathophysiology of human cerebral aneurysms.

  8. Autologous adventitial overlay method reinforces anastomoses in aortic surgery.

    Science.gov (United States)

    Minato, Naoki; Okada, Takayuki; Sumida, Tomohiko; Watanabe, Kenichi; Maruyama, Takahiro; Kusunose, Takashi

    2014-05-01

    In this study, we present an inexpensive and effective method for providing a secure and hemostatic anastomosis using autologous adventitia obtained from a dissected or aneurysmal wall. The resected aortic wall is separated between the adventitia and media, and a soft, 2 × 10-cm adventitial strip is overlaid to cover the anastomotic margin. A graft is sutured to the aortic stump. This autologous adventitial overlay method can inexpensively and strongly reinforce the anastomosis during aortic surgery for dissection or aneurysm and will contribute to anastomotic hemostasis and long-term stability.

  9. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts.

    Directory of Open Access Journals (Sweden)

    Eric C Martens

    2011-12-01

    Full Text Available Symbiotic bacteria inhabiting the human gut have evolved under intense pressure to utilize complex carbohydrates, primarily plant cell wall glycans in our diets. These polysaccharides are not digested by human enzymes, but are processed to absorbable short chain fatty acids by gut bacteria. The Bacteroidetes, one of two dominant bacterial phyla in the adult gut, possess broad glycan-degrading abilities. These species use a series of membrane protein complexes, termed Sus-like systems, for catabolism of many complex carbohydrates. However, the role of these systems in degrading the chemically diverse repertoire of plant cell wall glycans remains unknown. Here we show that two closely related human gut Bacteroides, B. thetaiotaomicron and B. ovatus, are capable of utilizing nearly all of the major plant and host glycans, including rhamnogalacturonan II, a highly complex polymer thought to be recalcitrant to microbial degradation. Transcriptional profiling and gene inactivation experiments revealed the identity and specificity of the polysaccharide utilization loci (PULs that encode individual Sus-like systems that target various plant polysaccharides. Comparative genomic analysis indicated that B. ovatus possesses several unique PULs that enable degradation of hemicellulosic polysaccharides, a phenotype absent from B. thetaiotaomicron. In contrast, the B. thetaiotaomicron genome has been shaped by increased numbers of PULs involved in metabolism of host mucin O-glycans, a phenotype that is undetectable in B. ovatus. Binding studies of the purified sensor domains of PUL-associated hybrid two-component systems in conjunction with transcriptional analyses demonstrate that complex oligosaccharides provide the regulatory cues that induce PUL activation and that each PUL is highly specific for a defined cell wall polymer. These results provide a view of how these species have diverged into different carbohydrate niches by evolving genes that target

  10. Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

    Directory of Open Access Journals (Sweden)

    Xinping Hao

    Full Text Available Age-related hearing loss (presbycusis is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old and aged (2-2.5 year-old mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the

  11. Genetics Home Reference: supravalvular aortic stenosis

    Science.gov (United States)

    ... usual. A thickened aorta is less flexible and resilient to the stress of constant blood flow and pumping of the heart. Over time, the wall of the aorta can become damaged. Aortic narrowing causes the heart to work harder to pump blood through the aorta, resulting ...

  12. Aortic Annular Enlargement during Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Selman Dumani

    2016-09-01

    Full Text Available In the surgery of aortic valve replacement is always attempted, as much as possible, to implant the larger prosthesis with the mains goals to enhance the potential benefits, to minimise transvalvular gradient, decrease left ventricular size and avoid the phenomenon of patient-prosthesis mismatch. Implantation of an ideal prosthesis often it is not possible, due to a small aortic annulus. A variety of aortic annulus enlargement techniques is reported to avoid patient-prosthesis mismatch. We present the case that has submitted four three times open heart surgery. We used Manouguian technique to enlarge aortic anulus with excellent results during the fourth time of surgery.

  13. Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm.

    Science.gov (United States)

    Tanaka, Hiroki; Zaima, Nobuhiro; Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki

    2015-01-01

    The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30-49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.

  14. Advancements in identifying biomechanical determinants for abdominal aortic aneurysm rupture.

    Science.gov (United States)

    Kontopodis, Nikolaos; Metaxa, Eleni; Papaharilaou, Yannis; Tavlas, Emmanouil; Tsetis, Dimitrios; Ioannou, Christos

    2015-02-01

    Abdominal aortic aneurysms are a common health problem and currently the need for surgical intervention is determined based on maximum diameter and growth rate criteria. Since these universal variables often fail to predict accurately every abdominal aortic aneurysms evolution, there is a considerable effort in the literature for other markers to be identified towards individualized rupture risk estimations and growth rate predictions. To this effort, biomechanical tools have been extensively used since abdominal aortic aneurysm rupture is in fact a material failure of the diseased arterial wall to compensate the stress acting on it. The peak wall stress, the role of the unique geometry of every individual abdominal aortic aneurysm as well as the mechanical properties and the local strength of the degenerated aneurysmal wall, all confer to rupture risk. In this review article, the assessment of these variables through mechanical testing, advanced imaging and computational modeling is reviewed and the clinical perspective is discussed.

  15. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  16. Abdominal aortic aneurysm

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000162.htm Abdominal aortic aneurysm To use the sharing features on this page, ... blood to the abdomen, pelvis, and legs. An abdominal aortic aneurysm occurs when an area of the aorta becomes ...

  17. Aortic growth rates in chronic aortic dissection

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, A.M. [Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center (United States)]. E-mail: ainekell@med.umich.edu; Quint, L.E. [Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center (United States); Nan, B. [School of Public Health, University of Michigan, Ann Arbor, Michigan (United States); Zheng, J. [School of Public Health, University of Michigan, Ann Arbor, Michigan (United States); Cronin, P. [Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center (United States); Deeb, G.M. [Division of Cardiac Surgery, University of Michigan Medical Center (United States); Williams, D.M. [Division of Vascular Interventional Imaging, University of Michigan Medical Center (United States)

    2007-09-15

    Aim: To determine and compare rates of descending aortic enlargement and complications in chronic aortic dissection with and without a proximal aortic graft. Methods and materials: Fifty-two patients with dissection involving the descending aorta and who had undergone at least two computed tomography (CT) examinations at our institution between November, 1993 and February, 2004 were identified, including 24 non-operated patients (four type A, 20 type B) and 28 operated patients (type A). CT examinations per patient ranged from two to 10, and follow-up ranged from 1-123 months (mean 49 months, median 38.5 months). On each CT image, the aortic short axis (SA), false lumen (FL), and true lumen (TL) diameters were measured at the longitudinal midpoint of the dissection and at the point of maximum aortic diameter. Complications were tabulated, including aortic rupture and aortic enlargement requiring surgery. Results: For non-operated patients, the midpoint and maximum point SA, TL, and FL diameters increased significantly over time. For operated patients, the midpoint and maximum point SA and FL diameters increased significantly over time. In both groups, aortic enlargement was predominantly due to FL expansion. Diameter increases in non-operated patients were significantly larger than those in operated patients. The rate of change in aortic diameter was constant, regardless of aortic size. Four non-operated and six operated patients developed aortic complications. Conclusions: In patients with a dissection involving the descending thoracic aorta, the FL increased in diameter over time, at a constant rate, and to a greater degree in non-operated patients (mostly type B) compared with operated patients (all type A)

  18. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    Science.gov (United States)

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

  19. Comparative study of abdominal and thoracic aortic aneurysms: their pathogenesis and a gingival fibroblasts-based ex vivo treatment.

    Science.gov (United States)

    Cherifi, Hafida; Gogly, Bruno; Loison-Robert, Ludwig-Stanislas; Couty, Ludovic; Ferré, François Côme; Nassif, Ali; Lafont, Antoine; Fournier, Benjamin Pj

    2015-01-01

    Aortic aneurysms (AAs) consist of slow proteolysis and loss of both collagen and elastin matrix in the aorta wall, leading to wall dilation, weakening and rupture in well-advanced lesions. This can occur in both abdominal aorta (Abdominal Aortic Aneurysm: AAA) and thoracic aorta (Thoracic Aortic Aneurysm: TAA). To date, no non-surgical therapy has been proposed to slow or stop AA progression. Previously published preclinical studies from our team using an aneurysm rabbit model showed a promising concept for treatment of AAs with gingival fibroblast (GFs) which are readily available cells. In this study, we investigated the possible tissue repair of human AAAs and TAAs using ex vivo models co-cultured with GFs. Histological analysis showed that TAA and AAA are two distinct pathologies. Both lesions presented destruction of the aorta wall, highly evidenced in AAA samples. The results have confirmed the presence of the bacterial Porphyromonas gingivalis (Pg) protein in all AAA samples, but not in TAA samples, indicating the possible role of an infectious factor in the developing and progression of AAA lesions compared to TAA. The co-culture of GFs with AA lesions shows increased expression of TIMP-1, the inhibitor of the aneurysm severity marker MMP-9. Our study indicates that GFs might ameliorate aorta wall reestablishment in both AA types by their regenerative and immunomodulatory capacities. It also demonstrates the possible infectious cause of AAA compared with TAA that may explain their different behavior.

  20. The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta

    Directory of Open Access Journals (Sweden)

    Butany Jagdish

    2003-11-01

    Full Text Available Abstract Purpose The goal of this work was to determine wall shear stress (WSS patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT from autopsy samples. Methods The WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens. Results The histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals, strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r2 = 0.3099; P = 0.0047. Conclusion Low WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

  1. Toxicology Study of Single-walled Carbon Nanotubes and Reduced Graphene Oxide in Human Sperm

    Science.gov (United States)

    Asghar, Waseem; Shafiee, Hadi; Velasco, Vanessa; Sah, Vasu R.; Guo, Shirui; El Assal, Rami; Inci, Fatih; Rajagopalan, Adhithi; Jahangir, Muntasir; Anchan, Raymond M.; Mutter, George L.; Ozkan, Mihrimah; Ozkan, Cengiz S.; Demirci, Utkan

    2016-08-01

    Carbon-based nanomaterials such as single-walled carbon nanotubes and reduced graphene oxide are currently being evaluated for biomedical applications including in vivo drug delivery and tumor imaging. Several reports have studied the toxicity of carbon nanomaterials, but their effects on human male reproduction have not been fully examined. Additionally, it is not clear whether the nanomaterial exposure has any effect on sperm sorting procedures used in clinical settings. Here, we show that the presence of functionalized single walled carbon nanotubes (SWCNT-COOH) and reduced graphene oxide at concentrations of 1–25 μg/mL do not affect sperm viability. However, SWCNT-COOH generate significant reactive superoxide species at a higher concentration (25 μg/mL), while reduced graphene oxide does not initiate reactive species in human sperm. Further, we demonstrate that exposure to these nanomaterials does not hinder the sperm sorting process, and microfluidic sorting systems can select the sperm that show low oxidative stress post-exposure.

  2. DNA methylation changes in human lung epithelia cells exposed to multi-walled carbon nanotubes.

    Science.gov (United States)

    Sierra, Marta I; Rubio, Laura; Bayón, Gustavo F; Cobo, Isabel; Menendez, Pablo; Morales, Paula; Mangas, Cristina; Urdinguio, Rocio G; Lopez, Virginia; Valdes, Adolfo; Vales, Gerard; Marcos, Ricard; Torrecillas, Ramon; Fernández, Agustin F; Fraga, Mario F

    2017-09-13

    Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO2NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO2NPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome.

  3. A Perspective Review on Numerical Simulations of Hemodynamics in Aortic Dissection

    Science.gov (United States)

    Wan Ab Naim, Wan Naimah; Ganesan, Poo Balan; Hashim, Shahrul Amry

    2014-01-01

    Aortic dissection, characterized by separation of the layers of the aortic wall, poses a significant challenge for clinicians. While type A aortic dissection patients are normally managed using surgical treatment, optimal treatment strategy for type B aortic dissection remains controversial and requires further evaluation. Although aortic diameter measured by CT angiography has been clinically used as a guideline to predict dilation in aortic dissection, hemodynamic parameters (e.g., pressure and wall shear stress), geometrical factors, and composition of the aorta wall are known to substantially affect disease progression. Due to the limitations of cardiac imaging modalities, numerical simulations have been widely used for the prediction of disease progression and therapeutic outcomes, by providing detailed insights into the hemodynamics. This paper presents a comprehensive review of the existing numerical models developed to investigate reasons behind tear initiation and progression, as well as the effectiveness of various treatment strategies, particularly the stent graft treatment. PMID:24672348

  4. Human chest wall function while awake and during halothane anesthesia. I. Quiet breathing.

    Science.gov (United States)

    Warner, D O; Warner, M A; Ritman, E L

    1995-01-01

    Data concerning chest wall configuration and the activities of the major respiratory muscles that determine this configuration during anesthesia in humans are limited. The aim of this study was to determine the effects of halothane anesthesia on respiratory muscle activity and chest wall shape and motion during spontaneous breathing. Six human subjects were studied while awake and during 1 MAC halothane anesthesia. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional fast computed tomography. Tidal changes in gas volume were measured by integrating respiratory gas flow, and the functional residual capacity was measured by a nitrogen dilution technique. While awake, ribcage expansion was responsible for 25 +/- 4% (mean +/- SE) of the total change in thoracic volume (delta Vth) during inspiration. Phasic inspiratory activity was regularly present in the diaphragm and parasternal intercostal muscles. Halothane anesthesia (1 MAC) abolished activity in the parasternal intercostal muscles and increased phasic expiratory activity in the abdominal muscles and lateral ribcage muscles. However, halothane did not significantly change the ribcage contribution to delta Vth (18 +/- 4%). Intrathoracic blood volume, measured by comparing changes in total thoracic volume and gas volume, increased significantly during inspiration both while awake and while anesthetized (by approximately 20% of delta Vth, P < 0.05). Halothane anesthesia significantly reduced the functional residual capacity (by 258 +/- 78 ml), primarily via an inward motion of the end-expiratory position of the ribcage. Although the diaphragm consistently changed shape, with a cephalad displacement of posterior regions and a caudad displacement of anterior regions, the diaphragm did not consistently contribute to the reduction in the functional residual capacity. Halothane anesthesia

  5. Idiopathic thoracic aortic aneurysm at pediatric age.

    Science.gov (United States)

    Marín-Manzano, E; González-de-Olano, D; Haurie-Girelli, J; Herráiz-Sarachaga, J I; Bermúdez-Cañete, R; Tamariz-Martel, A; Cuesta-Gimeno, C; Pérez-de-León, J

    2009-03-01

    A 6-year-old-boy presented with epigastric pain and vomiting over 1 year. Chest X-ray and esophagogastric transit showed a mediastinal mass. A chest computerized tomography angiogram demonstrated a descending thoracic aortic aneurysm. Analytical determinations carried out were all negative. The aneurysm was surgically repaired using a Dacron patch. The anatomopathological study described atherosclerotic lesions with calcifications, compatible with an atherosclerotic aneurysm wall. Aneurysms are uncommon in the pediatric population. Usually, no pathogenesis can be determined, and thus, such cases are grouped as idiopathic. Direct repair with or without patch is a therapeutic alternative in pediatric aneurysms and can allow the growth of the aortic circumference.

  6. Diffusion of Alexa Fluor 488-conjugated dendrimers in rat aortic tissue.

    Science.gov (United States)

    Cho, Brenda S; Roelofs, Karen J; Majoros, Istvan J; Baker, James R; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2006-11-01

    In this study, the distribution of labeled dendrimers in native and aneurysmal rat aortic tissue was examined. Adult male rats underwent infrarenal aorta perfusion with generation 5 (G5) acetylated Alexa Fluor 488-conjugated dendrimers for varying lengths of time. In a second set of experiments, rats underwent aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later. Aortic diameters were measured prior to and postelastase perfusion, and again on the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed, and mounted. Native aortas were harvested and viewed as negative controls. Aortic cross-sections were viewed and imaged using confocal microscopy. Dendrimers were quantified (counts/high-powered field). Results were evaluated by repeated measures ANOVA and Student's t-test. We found that in native aortas, dendrimers penetrated the aortic wall in all groups. For all perfusion times, fewer dendrimers were present as time between dendrimer perfusion and aortic harvest increased. Longer perfusion times resulted in increased diffusion of dendrimers throughout the aortic wall. By 24 h, the majority of the dendrimers were through the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion, diffused farther into the aortic wall than controls. In conclusion, this study documents labeled dendrimers delivered intra-arterially to native rat aortas in vivo, and the temporal diffusion of these molecules within the aortic wall. Increasing perfusion time and length of time prior to harvest resulted in continued dendrimer diffusion into the aortic wall. These preliminary data provide a novel mechanism whereby local inhibitory therapy may be delivered locally to aortic tissue.

  7. Human chest wall function while awake and during halothane anesthesia. II. Carbon dioxide rebreathing.

    Science.gov (United States)

    Warner, D O; Warner, M A

    1995-01-01

    Changes in the distribution of respiratory drive to different respiratory muscles may contribute to respiratory depression produced by halothane. The aim of this study was to examine factors that are responsible for halothane-induced depression of the ventilatory response to carbon dioxide rebreathing. In six human subjects, respiratory muscle activity in the parasternal intercostal, abdominal, and diaphragm muscles was measured using fine-wire electromyography electrodes. Chest wall motion was determined by respiratory impedance plethysmography. Electromyography activities and chest wall motion were measured during hyperpnea produced by carbon dioxide rebreathing while the subjects were awake and during 1 MAC halothane anesthesia. Halothane anesthesia significantly reduced the slope of the response of expiratory minute ventilation to carbon dioxide (from 2.88 +/- 0.73 (mean +/- SE) to 2.01 +/- 0.45 l.min-1.mmHg-1). During the rebreathing period, breathing frequency significantly increased while awake (from 10.3 +/- 1.4 to 19.7 +/- 2.6 min-1, P awake and anesthetized in four of the six subjects. Halothane anesthesia enhances the rebreathing response of neural drive to the primary respiratory muscle, the diaphragm. These findings provide direct evidence that, at the dose examined in this study, halothane-induced respiratory depression is caused by alterations in the distribution and timing of neural drive to the respiratory muscles, rather than a global depression of respiratory motoneuron drive.

  8. Textural feature selection for enhanced detection of stationary humans in through-the-wall radar imagery

    Science.gov (United States)

    Chaddad, A.; Ahmad, F.; Amin, M. G.; Sevigny, P.; DiFilippo, D.

    2014-05-01

    Feature-based methods have been recently considered in the literature for detection of stationary human targets in through-the-wall radar imagery. Specifically, textural features, such as contrast, correlation, energy, entropy, and homogeneity, have been extracted from gray-level co-occurrence matrices (GLCMs) to aid in discriminating the true targets from multipath ghosts and clutter that closely mimic the target in size and intensity. In this paper, we address the task of feature selection to identify the relevant subset of features in the GLCM domain, while discarding those that are either redundant or confusing, thereby improving the performance of feature-based scheme to distinguish between targets and ghosts/clutter. We apply a Decision Tree algorithm to find the optimal combination of co-occurrence based textural features for the problem at hand. We employ a K-Nearest Neighbor classifier to evaluate the performance of the optimal textural feature based scheme in terms of its target and ghost/clutter discrimination capability and use real-data collected with the vehicle-borne multi-channel through-the-wall radar imaging system by Defence Research and Development Canada. For the specific data analyzed, it is shown that the identified dominant features yield a higher classification accuracy, with lower number of false alarms and missed detections, compared to the full GLCM based feature set.

  9. Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

    Science.gov (United States)

    Margolis, L.; Hatfill, S.; Chuaqui, R.; Vocke, C.; Emmert-Buck, M.; Linehan, W. M.; Duray, P. H.

    1999-01-01

    PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

  10. Sex differences in abdominal aortic aneurysm: the role of sex hormones.

    Science.gov (United States)

    Makrygiannis, Georgios; Courtois, Audrey; Drion, Pierre; Defraigne, Jean-Olivier; Kuivaniemi, Helena; Sakalihasan, Natzi

    2014-11-01

    Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in men, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature, we examined human and animal in vivo and in vitro studies to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17β-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in men and women, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.

  11. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  12. Valvular Aortic Stenosis: A Proteomic Insight

    Directory of Open Access Journals (Sweden)

    Fernando Vivanco

    2010-02-01

    Full Text Available Calcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. In the present work we describe a rapid, reproducible and effective method to carry out proteomic analysis of stenotic human valves by conventional 2-DE and 2D-DIGE, minimizing the interference due to high calcium concentrations. Furthermore, the protocol permits the aortic stenosis proteome to be analysed, advancing our knowledge in this area. Summary: Until recently, aortic stenosis (AS was considered a passive process secondary to calcium deposition in the aortic valves. However, it has recently been highlighted that the risk factors associated with the development of calcified AS in the elderly are similar to those of coronary artery disease. Furthermore, degenerative AS shares histological characteristics with atherosclerotic plaques, leading to the suggestion that calcified aortic valve disease is a chronic inflammatory process similar to atherosclerosis. Nevertheless, certain data does not fit with this theory making it necessary to further study this pathology. The aim of this study is to develop an effective protein extraction protocol for aortic stenosis valves such that proteomic analyses can be performed on these structures. In the present work we have defined a rapid, reproducible and effective method to extract proteins and that is compatible with 2-DE, 2D-DIGE and MS techniques. Defining the protein profile of this tissue is an important and challenging task that will help to understand the mechanisms of physiological/pathological processes in aortic stenosis valves.

  13. Unexpected death caused by rupture of a dilated aorta in an adult male with aortic coarctation.

    Science.gov (United States)

    Leth, Peter Mygind; Knudsen, Peter Thiis

    2015-09-01

    Aortic coarctation (AC) is a congenital aortic narrowing. We describe for the first time the findings obtained by unenhanced post mortem computed tomography (PMCT) in a case where the death was caused by cardiac tamponade from a ruptured aneurysmal dilatation of the ascending aorta and the aortic arch without dissection combined with aortic coarctation. The patient, a 46-year-old man, was found dead at home. PMCT showed haemopericardium and dilatation of the ascending aorta and the aortic arch. This appearance led to the mistaken interpretation that the images represented a dissecting aneurysm. The autopsy showed instead a thin-walled and floppy dilatation of the ascending aorta and aortic arch with a coarctation just proximal to the ligamentum arteriosum. A longitudinal tear was found in the posterior aortic wall just above the valves. Blood in the surrounding soft tissue intersected with a large haematoma (1000ml) in the pericardial sac. Cardiac hypertrophy (556g) was observed in the patient, though no other cardiovascular abnormalities were found. Histological analysis showed cystic medial necrosis of the ascending aortic wall. A ruptured aneurysmal dilatation of the ascending aorta and the aortic arch without aortic dissection associated with AC is an uncommon cause of haemopericardium that has only been described a few times before. The case is discussed in relation to other reported cases and in the context of the present understanding of this condition.

  14. Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation

    Science.gov (United States)

    Valente, Acrisio Sales; Alencar, Polyanna; Santos, Alana Neiva; Lobo, Roberto Augusto de Mesquita; de Mesquita, Fernando Antônio; Guimarães, Aloyra Guedis

    2013-01-01

    The supravalvular aortic stenosis is a rare congenital heart defect being very uncommon in adults. We present a case of supravalvular aortic stenosis in adult associated with anomalies of the aortic arch vessels and aortic regurgitation, which was submitted to aortic valve replacement and arterioplasty of the ascending aorta with a good postoperative course. PMID:24598962

  15. The Genetic Basis of Aortic Aneurysm

    Science.gov (United States)

    Lindsay, Mark E.; Dietz, Harry C.

    2014-01-01

    Gene identification in human aortic aneurysm conditions is proceeding at a rapid pace and the integration of pathogenesis-based management strategies in clinical practice is an emerging reality. Human genetic alterations causing aneurysm involve diverse gene products including constituents of the extracellular matrix, cell surface receptors, intracellular signaling molecules, and elements of the contractile cytoskeleton. Animal modeling experiments and human genetic discoveries have extensively implicated the transforming growth factor-β (TGF-β) cytokine-signaling cascade in aneurysm progression, but mechanistic links between many gene products remain obscure. This chapter will integrate human genetic alterations associated with aortic aneurysm with current basic research findings in an attempt to form a reconciling if not unifying model for hereditary aortic aneurysm. PMID:25183854

  16. Multi wall carbon nanotubes induce oxidative stress and cytotoxicity in human embryonic kidney (HEK293) cells.

    Science.gov (United States)

    Reddy, Anreddy Rama Narsimha; Reddy, Yellu Narsimha; Krishna, Devarakonda Rama; Himabindu, Vurimindi

    2010-06-04

    The present study was aimed at evaluating the potential toxicity and the general mechanism involved in multi wall carbon nanotubes (MWCNT)-induced cytotoxicity using human embryonic kidney cell line (HEK293) cells. Two multi wall carbon nanotubes (coded as MWCNT1, size: 90-150nm and MWCNT2, size: 60-80nm) used in this study are MWCNT1 (produced by the electric arc method and size of the nanotubes was 90-150nm) and MWCNT2 (produced by the chemical vapor deposition method with size of 60-80nm). To elucidate the possible mechanisms of MWCNT induced cytotoxicity, cell viability, mitochondrial function (MTT assay), cell membrane damage (LDH assay), reduced glutathione (GSH), interleukin-8 (IL-8) and lipid peroxidation levels were quantitatively assessed under carbon nanotubes exposed (48h) conditions. Exposure of different sizes of two carbon nanotubes at dosage levels between 3 and 300mug/ml decreased cell viability in a concentration dependent manner. The IC(50) values (concentration of nanoparticles to induce 50% cell mortality) of two (MWCNT1, MWCNT2) nanoparticles were found as 42.10 and 36.95mug/ml. Exposure of MWCNT (10-100mug/ml) to HEK cells resulted in concentration dependent cell membrane damage (as indicated by the increased levels of LDH), increased production of IL-8, increased TBARS and decreased intracellular glutathione levels. The cytotoxicity and oxidative stress was significantly more in MWCNT2 exposed cells than MWCNT1. In summary, exposure of carbon nanotubes resulted in a concentration dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.

  17. Intramural aortic hematomas; Intramurale Haematome der Aorta

    Energy Technology Data Exchange (ETDEWEB)

    Raab, B.W.; Vosshenrich, R.; Fischer, U.; Funke, M.; Grabbe, E. [Goettingen Univ. (Germany). Abt. fuer Roentgendiagnostik

    2001-08-01

    Intramural hematomas (IMH) are regarded as a hemorrhage into the aortic wall. In general a traumatic form can be differentiated from a spontaneous non-traumatic. There is a predisposition of IMH with arterial hypertension and mesoectodermal dysplastic syndromes. The diagnosis is established with the clinical presentation in combination with the findings of different imaging modalities. Acute and subacute discomfort associated with a tendency of collaps are considered as typical presenting complaints. A semicircular or concentric thickening of the aortic wall with the absence of blood flow or a dissection membran are typical findings in transesophageal echocardiography, computed tomography and magnetic resonance tomography. From a differential diagnostic point of view a distinction from atherosclerotic wall changes, intraluminal thrombi and inflammatory aortic diseases is essential. The IMH is considered as an early presentation of aortic dissection, put into and treated according to the Stanford classification. In the course of natural history an IMH can disappear, rupture or progress into a classic aortic dissection. (orig.) [German] Das intramurale Haematom (IMH) ist eine Einblutung in die Aortenwand. Grundsaetzlich kann zwischen traumatischer Genese und einer atraumatischen spontanen Form unterschieden werden. Praedisponierend sind arterielle Hypertension und mesoektodermale Dysplasiesyndrome. Die Diagnose ergibt sich aus der Klinik und den Befunden in den bildgebenden Verfahren. Zu den klinischen Symptomen zaehlen akut oder subakut auftretende Schmerzen, assoziiert mit einer Kollapsneigung. Typische Befunde in der transoesophagealen Echokardiographie, der Computer- oder der Magnetresonanztomographie sind eine halbmondfoermige oder konzentrische Wandverdickung der Aorta ohne Nachweis von Blutfluss oder einer Dissektionsmembran mit Dichtewerten bzw. Signalintensitaeten in Abhaengigkeit vom Alter der Einblutung. Differenzialdiagnostisch ist eine Abgrenzung

  18. Inhibitory role of Notch1 in calcific aortic valve disease.

    Directory of Open Access Journals (Sweden)

    Asha Acharya

    Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

  19. Nature and origin of the neointima in whole vessel wall organ culture of the human saphenous vein

    NARCIS (Netherlands)

    Slomp, J.; Gittenberger - Groot, A.C. de; Munsteren, J.C. van; Huysmans, H.A.; Bockel, J.H. van; Hinsbergh, V.W.M. van; Poelmann, R.E.

    1996-01-01

    Intimal proliferation is a characteristic feature of arteriosclerosis. Whole vessel wall organ culture systems have been developed to study the early stages of neointima formation. We have cultured a large number of explants of human saphenous vein specimens for several weeks, and have identified th

  20. Cell wall trapping of autocrine peptides for human G-protein-coupled receptors on the yeast cell surface.

    Directory of Open Access Journals (Sweden)

    Jun Ishii

    Full Text Available G-protein-coupled receptors (GPCRs regulate a wide variety of physiological processes and are important pharmaceutical targets for drug discovery. Here, we describe a unique concept based on yeast cell-surface display technology to selectively track eligible peptides with agonistic activity for human GPCRs (Cell Wall Trapping of Autocrine Peptides (CWTrAP strategy. In our strategy, individual recombinant yeast cells are able to report autocrine-positive activity for human GPCRs by expressing a candidate peptide fused to an anchoring motif. Following expression and activation, yeast cells trap autocrine peptides onto their cell walls. Because captured peptides are incapable of diffusion, they have no impact on surrounding yeast cells that express the target human GPCR and non-signaling peptides. Therefore, individual yeast cells can assemble the autonomous signaling complex and allow single-cell screening of a yeast population. Our strategy may be applied to identify eligible peptides with agonistic activity for target human GPCRs.

  1. Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in apolipoprotein-E-deficient mice.

    Science.gov (United States)

    Wu, Wen-Huey; Wang, Shu-Huei; Kuan, I-I; Kao, Ya-Shi; Wu, Pei-Jhen; Liang, Chan-Jung; Chien, Hsiung-Fei; Kao, Chiu-Hua; Huang, Ching-Jang; Chen, Yuh-Lien

    2010-09-01

    Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.

  2. The in vitro protection of human decay accelerating factor and hDAF/heme oxygenase-1 transgenes in porcine aortic endothelial cells against sera of Formosan macaques.

    Science.gov (United States)

    Tu, C-F; Tai, H-C; Wu, C-P; Ho, L-L; Lin, Y-J; Hwang, C-S; Yang, T-S; Lee, J-M; Tseng, Y-L; Huang, C-C; Weng, C-N; Lee, P-H

    2010-01-01

    To mitigate hyperacute rejection, pigs have been generated with alpha-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC. Copyright 2010 Elsevier Inc. All rights reserved.

  3. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells

    Science.gov (United States)

    Patel, Vishal; Carrion, Katrina; Hollands, Andrew; Hinton, Andrew; Gallegos, Thomas; Dyo, Jeffrey; Sasik, Roman; Leire, Emma; Hardiman, Gary; Mohamed, Salah A.; Nigam, Sanjay; King, Charles C.; Nizet, Victor; Nigam, Vishal

    2015-01-01

    Bicuspid aortic valves calcify at a significantly higher rate than normal aortic valves, a process that involves increased inflammation. Because we have previously found that bicuspid aortic valve experience greater stretch, we investigated the potential connection between stretch and inflammation in human aortic valve interstitial cells (AVICs). Microarray, quantitative PCR (qPCR), and protein assays performed on AVICs exposed to cyclic stretch showed that stretch was sufficient to increase expression of interleukin and metalloproteinase family members by more than 1.5-fold. Conditioned medium from stretched AVICs was sufficient to activate leukocytes. microRNA sequencing and qPCR experiments demonstrated that miR-148a-3p was repressed in both stretched AVICs (43% repression) and, as a clinical correlate, human bicuspid aortic valves (63% reduction). miR-148a-3p was found to be a novel repressor of IKBKB based on data from qPCR, luciferase, and Western blot experiments. Furthermore, increasing miR-148a-3p levels in AVICs was sufficient to decrease NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and NF-κB target gene expression. Our data demonstrate that stretch-mediated activation of inflammatory pathways is at least partly the result of stretch-repression of miR-148a-3p and a consequent failure to repress IKBKB. To our knowledge, we are the first to report that cyclic stretch of human AVICs activates inflammatory genes in a tissue-autonomous manner via a microRNA that regulates a central inflammatory pathway.—Patel, V., Carrion, K., Hollands, A., Hinton, A., Gallegos, T., Dyo, J., Sasik, R., Leire, E., Hardiman, G., Mohamed, S. A., Nigam, S., King, C. C., Nizet, V., Nigam V. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells. PMID:25630970

  4. Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs).

    Science.gov (United States)

    Sharma, Monita; Nikota, Jake; Halappanavar, Sabina; Castranova, Vincent; Rothen-Rutishauser, Barbara; Clippinger, Amy J

    2016-07-01

    The increased production and use of multi-walled carbon nanotubes (MWCNTs) in a diverse array of consumer, medical, and industrial applications have raised concerns about potential human exposure to these materials in the workplace and ambient environments. Inhalation is a primary route of exposure to MWCNTs, and the existing data indicate that they are potentially hazardous to human health. While a 90-day rodent inhalation test (e.g., OECD Test No. 413: subchronic inhalation toxicity: 90-day study or EPA Health Effects Test Guidelines OPPTS 870.3465 90-day inhalation toxicity) is recommended by the U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics for MWCNTs (and other CNTs) if they are to be commercially produced (Godwin et al. in ACS Nano 9:3409-3417, 2015), this test is time and cost-intensive and subject to scientific and ethical concerns. As a result, there has been much interest in transitioning away from studies on animals and moving toward human-based in vitro and in silico models. However, given the multiple mechanisms of toxicity associated with subchronic exposure to inhaled MWCNTs, a battery of non-animal tests will likely be needed to evaluate the key endpoints assessed by the 90-day rodent study. Pulmonary fibrosis is an important adverse outcome related to inhalation exposure to MWCNTs and one that the non-animal approach should be able to assess. This review summarizes the state-of-the-science regarding in vivo and in vitro toxicological methods for predicting MWCNT-induced pulmonary fibrosis.

  5. FBN1 Mutations in Patients With Descending Thoracic Aortic Dissections

    Science.gov (United States)

    Brautbar, Ariel; LeMaire, Scott A.; Franco, Luis M.; Coselli, Joseph S.; Milewicz, Dianna M.; Belmont, John W.

    2013-01-01

    Aortic aneurysm and dissection cause significant morbidity and mortality. There are several known single gene disorders that predispose to isolated aortic disease and eventually aneurysm and dissection. FBN1 mutations are associated with multiple clinical phenotypes, including Marfan syndrome (MFS), MASS phenotype, and familial ectopia lentis, but rarely with isolated aortic aneurysm and dissection. In this report, we describe three patients who presented with primary descending thoracic aortic dissection and who were found to have an FBN1 mutation. None of the patients fulfilled clinical criteria for the diagnosis of MFS, and all had few or none of the skeletal features typical of the condition. Two patients had a history of long-term hypertension, and such a history was suspected in the third patient. These observations suggest that some individuals with FBN1 mutations have significant aortic disease involvement of other systems that is typical of FBN1 mutation-related syndromes. Superimposed risk factors, such as hypertension, may weaken the aortic wall and eventually lead to aortic dissection. Given that the cost continues to decrease, we suggest that diagnostic DNA sequencing for FBN1 mutations in patients with thoracic aortic aneurysms and dissection may be a practical clinical step in evaluating such patients and at-risk family members. PMID:20082464

  6. Aortic Remodeling Following Transverse Aortic Constriction in Mice is Attenuated with AT1 Receptor Blockade

    Science.gov (United States)

    Kuang, Shao-Qing; Geng, Liang; Prakash, Siddharth K.; Cao, Jiu-Mei; Guo, Steven; Villamizar, Carlos; Kwartler, Callie S.; Ju, Xiaoxi; Brasier, Allan R.; Milewicz, Dianna M.

    2016-01-01

    Objective Although hypertension is the most common risk factor for thoracic aortic diseases, it is not understood how increased pressures on the ascending aorta lead to aortic aneurysms. We investigated the role of Ang II type 1 (AT1) receptor activation in ascending aortic remodeling in response to increased biomechanical forces using a transverse aortic constriction (TAC) mouse model. Approach and Results Two weeks after TAC, the increased biomechanical pressures led to ascending aortic dilatation, aortic wall thickening and medial hypertrophy. Significant adventitial hyperplasia and inflammatory responses in TAC ascending aortas were accompanied by increased adventitial collagen, elevated inflammatory and proliferative markers, and increased cell density due to accumulation of myofibroblasts and macrophages. Treatment with losartan significantly blocked TAC induced vascular inflammation and macrophage accumulation. However, losartan only partially prevented TAC induced adventitial hyperplasia, collagen accumulation and ascending aortic dilatation. Increased Tgfb2 expression and phosphorylated-Smad2 staining in the medial layer of TAC ascending aortas was effectively blocked with losartan. In contrast, the increased Tgfb1 expression and adventitial phospho-Smad2 staining were only partially attenuated by losartan. In addition, losartan significantly blocked Erk activation and ROS production in the TAC ascending aorta. Conclusions Inhibition of the AT1 receptor using losartan significantly attenuated the vascular remodeling associated with TAC but did not completely block the increased TGF- β1 expression, adventitial Smad2 signaling and collagen accumulation. These results help to delineate the aortic TGF-β signaling that is dependent and independent of the AT1 receptor after TAC. PMID:23868934

  7. Advanced glycation end products promote human aortic smooth muscle cell calcification in vitro via activating NF-κB and down-regulating IGF1R expression

    Institute of Scientific and Technical Information of China (English)

    Yi WANG; Zhen-yu ZHANG; Xiao-qing CHEN; Xiang WANG; Heng CAO; Shao-wen LIU

    2013-01-01

    Aim:To investigate the effects of advanced glycation end products (AGEs) on calcification in human aortic smooth muscle cells (HASMCs) in vitro and the underlying mechanisms.Methods:AGEs were artificially prepared.Calcification of HASMCs was induced by adding inorganic phosphate (Pi,2 mmol/L) in the media,and observed with Alizarin red staining.The calcium content in the supernatant was measured using QuantiChrome Calcium Assay Kit.Expression of the related mRNAs and proteins was analyzed using real-time PCR and Western blot,respectively.Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NF-κB to the putative IGF1R promoter.Results:AGEs (100 μg/mL) significantly enhanced Pi-induced calcification and the levels of osteocalcin and Cbfα1 in HASMCs.Furthermore,the treatment decreased the expression of insulin-like growth factor 1 receptor (IGF1R).Over-expression of IGF1R in HASMCs suppressed the AGEs-induced increase in calcium deposition.When IGF1R expression was knocked down in HASMCs,AGEs did not enhance the calcium deposition.Meanwhile,AGEs time-dependently decreased the amounts of IκBα and Flag-tagged p65 in the cytoplasmic extracts,and increased the amount of nuclear p65 in HASMCs.In the presence of NF-κB inhibitor PDTC (50 μmol/L),the AGEs-induced increase in calcium deposition was blocked.Over-expression of p65 significantly enhanced Pi-induced mineralization,but suppressed IGF1R mRNA level.Knockdown of p65 suppressed the AGEs-induced increase in calcium deposition,and rescued the IGF1R expression.The ChIP analysis revealed that NF-κB bound the putative IGF1R promoter at position-230 to-219 bp.The inhibition of IGF1R by NF-κB was abolished when IGF1R reporter plasmid contained mutated binding sequence for NF-κB or an NF-κB reporter vector.Conclusion:The results demonstrate that AGEs promote calcification of human aortic smooth muscle cells in vitro via activation of NF-κB and down-regulation of IGF1R expression.

  8. Unusual presenting of acute aortic dissection due to penetrating atheromatous ulcer.

    Science.gov (United States)

    Atas, Halil; Durmus, Erdal; Sunbul, Murat; Birkan, Yasar; Ozben, Beste

    2014-07-01

    Penetrating atheromatous ulcer (PAU) is an atherosclerotic ulcer penetrating the internal elastic lamina of the aortic wall causing a hematoma within the media layer of aorta. They are commonly located in the descending aorta of the elderly and hypertensive patients. They may rarely be complicated by aortic dissection. We report a relative young normotensive patient presenting with acute aortic dissection due to PAU located in the ascending aorta.

  9. Commercial single-walled carbon nanotubes effects in fibrinolysis of human umbilical vein endothelial cells.

    Science.gov (United States)

    Rodríguez-Yáñez, Yury; Bahena-Uribe, Daniel; Chávez-Munguía, Bibiana; López-Marure, Rebeca; González-Monroy, Stuart; Cisneros, Bulmaro; Albores, Arnulfo

    2015-08-01

    Recent studies have demonstrated that carbon nanotubes (CNTs) induce platelet aggregation, endothelial dysfunction and vascular thrombosis. However, there is little information on the effects of CNTs on fibrinolysis. We investigated the role of pristine-commercial single-walled carbon nanotubes (SWCNTs) with <3% Co content in fibrinolysis and their contribution to the induction of pro-thrombotic processes in human vein endothelial cells (HUVEC). SWCNTs alone produced concentration-dependent oxidation, as measured by a dithiothreitol oxidation assay. Internalized SWCNTs were located in HUVEC treated with 25 μg/ml using transmission electron microscopy, whereas treatment with 50 μg/ml compromised cell viability, and oxidative stress increased significantly at 5 μg/ml. The study showed that in HUVEC treated with 25 μg SWCNT/ml, fibrinolysis-related gene expression and protein levels had increased by 3-12 h after treatment (serpine-1: 13-fold; PLAT: 11-fold and PLAU: 2-fold), but only the PAI-1 protein was increased (1.5-fold), whereas tissue and urokinase plasminogen activator proteins (tPA and uPA, respectively) tended to decrease. In summary, pristine SWCNTs treatment resulted in evident HUVEC damage caused by cell fiber contact, internalization, and oxidative stress due to contaminant metals. The generation of endothelial dysfunction, as shown by the altered expression of genes and proteins involved in fibrinolysis, suggest that SWCNTs display pro-thrombotic effects.

  10. Evaluation of aortic stiffness (aortic pulse-wave velocity) before and after elective abdominal aortic aneurysm repair procedures: a pilot study.

    Science.gov (United States)

    Paraskevas, Kosmas I; Bessias, Nikolaos; Psathas, Chrysovalantis; Akridas, Konstantinos; Dragios, Theodoros; Nikitas, Georgios; Andrikopoulos, Vassilios; Mikhailidis, Dimitri P; Kyriakides, Zenon S

    2009-12-09

    The main clinical criterion for abdominal aortic aneurysm (AAA) repair operations is an AAA diameter >/=5.5 cm. When AAAs increase in size, specific changes occur in the mechanical properties of the aortic wall. Pulse-wave velocity (PWV) has been used as an indicator of vascular stiffness. A low PWV may predict AAA rupture risk and is an early predictor of cardiovascular mortality. We investigated the prognostic value of PWV before and after elective AAA repair procedures. Twenty four patients scheduled for an open AAA repair underwent a preoperative carotid-femoral aortic PWV measurement. A second aortic PWV measurement was carried out 6 months postoperatively. The mean aortic PWV increased from 7.84 +/- 1.85 preoperatively to 10.08 +/- 1.57 m/sec 6 months postoperatively (mean change: 2.25; 95% confidence interval 1.4 to 3.1 m/sec; p<0.0001). The preprocedural PWV measurement did not correlate with AAA diameter (Spearman's rank correlation coefficient rho=0.12; p=0.59). Whether the increase in aortic PWV postoperatively suggests a decreased cardiovascular risk following AAA repair remains to be established. Aortic PWV should also be investigated as an adjunct tool for assessing AAA rupture risk.

  11. Conservative management of chronic aortic dissection with underlying aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Mohammad Yusuf Beebeejaun

    2013-01-01

    Full Text Available Aortic dissection is one of the most common aortic emergencies affecting around 2000 Americans each year. It usually presents in the acute state but in a small percentage of patients aortic dissections go unnoticed and these patients survive without any adequate therapy. With recent advances in medical care and diagnostic technologies, aortic dissection can be successfully managed through surgical or medical options, consequently increasing the related survival rate. However, little is known about the optimal long-term management of patients suffering from chronic aortic dissection. The purpose of the present report is to review aortic dissection, namely its pathology and the current diagnostic tools available, and to discuss the management options for chronic aortic dissection, infiltrates or pleural effusions. Other tion. We report a patient in which chronic aortic dissection presented with recurring episodes of vomiting and also discuss the management plan of our patient who had a chronic aortic dissection as well as an underlying aortic aneurysm.

  12. Distribution of selected elements in calcific human aortic valves studied by microscopy combined with SR-μXRF: influence of lipids on progression of calcification.

    Science.gov (United States)

    Lis, Grzegorz J; Czapla-Masztafiak, Joanna; Kwiatek, Wojciech M; Gajda, Mariusz; Jasek, Ewa; Jasinska, Malgorzata; Czubek, Urszula; Borchert, Manuela; Appel, Karen; Nessler, Jadwiga; Sadowski, Jerzy; Litwin, Jan A

    2014-12-01

    Calcified heart valves display a significant imbalance in tissue content of trace and essential elements. The valvular calcification is an age-related process and there are data suggesting involvement of lipids. We studied elemental composition and lipid distribution in three distinct regions of calcified human aortic valves, representing successive stages of the calcific degeneration: normal, thickened (early lesion) and calcified (late lesion), using SR-μXRF (Synchrotron Radiation Micro X-Ray Fluorescence) for elemental composition and Oil Red O (ORO) staining for demonstration of lipids. Two-dimensional SR-μXRF maps and precise point spectra were compared with histological stainings on consecutive valve sections to prove topographical localization and colocalization of the examined elements and lipids. In calcified valve areas, accumulation of calcium and phosphorus was accompanied by enhanced concentrations of strontium and zinc. Calcifications preferentially developed in lipid-rich areas of the valves. Calcium concentration ratio between lipid-rich and lipid-free areas was not age-dependent in early lesions, but showed a significant increase with age in late lesions, indicating age-dependent intensification of lipid involvement in calcification process. The results suggest that mechanisms of calcification change with progression of valve degeneration and with age.

  13. Evaluation of Distensibility and Stiffness of Ascending Aortic Aneurysm using Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Kaushal Kishore Tiwari

    2016-12-01

    Conclusions: MRI measurement of aortic diameters, distensibility, and flow wave velocity is an easy, reliable and reproducible technique. Distensibility and pulse wave velocity define the elasticity of the aorta. We have observed that elasticity of aortic wall is decreased in ascending aorta aneurysm patients. Keywords: ascending aorta aneurysm; distensibility; pulse wave velocity; MRI. | PubMed

  14. An increase in the threshold of citric acid-induced cough during chest wall vibration in healthy humans.

    Science.gov (United States)

    Kondo, T; Kobayashi, I; Hayama, N; Ohta, Y

    1998-10-01

    This study tested the hypothesis that the afferent input from the respiratory muscles may be involved in the neural mechanisms inducing cough responses. Coughing was evoked in conscious healthy humans by the inhalation of citric acid aerosol of several concentrations either during or not during chest wall vibration (100 Hz) at the right second intercostal space or during vibration of the right thigh. The mean threshold citric acid concentration to induce coughing was significantly higher during chest wall vibration (geometric mean, 131.8 mg/ml) than without vibration (75.9 mg/ml). Vibration after topical anesthesia of the chest wall skin did not significantly change the threshold concentration of citric acid. The threshold citric acid concentration during vibration of the right thigh did not significantly differ from that without vibration. We concluded that inputs from the chest wall afferent, presumably from the intercostal muscle or costovertebral joint, may have an inhibitory effect on the initiation of coughing at the higher neural structure in conscious humans.

  15. Heritable retinoblastoma and accelerated aortic valve disease

    Science.gov (United States)

    Abeyratne, L R; Kingston, J E; Onadim, Z; Dubrey, S W

    2013-01-01

    Heritable retinoblastoma is associated with a germline mutation in the tumour suppressor gene RBI. The Rb protein (pRb) arises from the RB1 gene, which was the first demonstrated cancer susceptibility gene in humans. 1 Second primary malignancies are recognised complications of retinoblastoma. Furthermore, pRb is implicated in valve remodelling in calcific aortic valve disease. 2 3 We report a family with hereditary retinoblastoma and associated secondary primary malignancies. There are two interesting aspects to this family. The first is the concept of ‘cancer susceptibility genes’; the RBI gene being the first reported in humans. A further feature of note is that two family members also have bicuspid aortic valves. We discuss a potential association between the gene defect responsible for retinoblastoma (with its associated propensity for further malignancies) and accelerated deterioration of the bicuspid aortic valve in the proband carrying this gene defect. PMID:23595191

  16. Assessment of vascular contrast and wall motion of the aortic root and ascending aorta on MDCT angiography: dual-source high-pitch vs non-gated single-source acquisition schemes

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, Jared D.; Seaman, Danielle M.; Lungren, Matthew P.; Hurwitz, Lynne M.; Boll, Daniel T. [Duke University Medical Center, Department of Radiology, Durham, NC (United States)

    2014-05-15

    This retrospective study assessed whether dual-source high-pitch computed tomographic angiography (CTA) offered advantages over single-source standard-pitch techniques in the evaluation of the ascending aorta. Twenty patients who received both thoracic dual-source high-pitch and single-source standard-pitch CTAs within 1 year were assessed. Dual-source CTAs were performed; standard-pitch imaging used dose-modulated 120 kVp/150 mAs and 0.8 pitch compared with high-pitch protocols employing dose-modulated 120 kVp/250 mAs and 2.4 target pitch. Radiation dose was documented. Contrast-to-noise ratios (CNRs) at sinuses of the Valsalva (CNR{sub Valsalva}) and ascending aorta (CNR{sub Aorta}) were calculated. Dose/CNR for each technique was compared with paired t-tests. Motion at aortic valve, aortic root and ascending aorta were assessed with four-point scales and Mann-Whitney U tests; longitudinal extension of motion was compared with paired t-tests. Significantly lower motion scores for high-pitch, compared with standard-pitch acquisitions for aortic annulus, 0 vs. 2, aortic root, 0 vs. 3, and ascending aorta, 0 vs. 2, were achieved. Significantly reduced longitudinal extension of motion at aortic root, 4.9 mm vs 15.7 mm, and ascending aorta, 4.9 mm vs 21.6 mm, was observed. Contrast was not impacted: CNR{sub Valsalva}, 45.6 vs 46.3, and CNR{sub Aorta}, 45.3 vs 47.1. CTDI{sub vol} was significantly decreased for high-pitch acquisitions, 13.9 mGy vs 15.8 mGy. Dual-source high-pitch CTAs significantly decreased motion artefact without negatively impacting vascular contrast and radiation dose. circle Dual-source high-pitch CTA significantly decreased motion artefact of the ascending aorta. circle Dual-source high-pitch CTA did not negatively impact on vascular contrast. circle Dual-source high-pitch CTA significantly decreased radiation dose compared with single-source standard-pitch acquisitions. (orig.)

  17. Reproducibility of ECG-gated Ultrasound Diameter Assessment of Small Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Bredahl, K; Eldrup, N; Meyer, C

    2013-01-01

    No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation....

  18. Transcriptional (ChIP-Chip Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Matthew C. Pahl

    2015-05-01

    Full Text Available We investigated transcriptional control of gene expression in human abdominal aortic aneurysm (AAA. We previously identified 3274 differentially expressed genes in human AAA tissue compared to non-aneurysmal controls. Four expressed transcription factors (ELF1, ETS2, STAT5 and RUNX1 were selected for genome-wide chromatin immunoprecipitation. Transcription factor binding was enriched in 4760 distinct genes (FDR < 0.05, of which 713 were differentially expressed in AAA. Functional classification using Gene Ontology (GO, KEGG, and Network Analysis revealed enrichment in several biological processes including “leukocyte migration” (FDR = 3.09 × 10−05 and “intracellular protein kinase cascade” (FDR = 6.48 × 10−05. In the control aorta, the most significant GO categories differed from those in the AAA samples and included “cytoskeleton organization” (FDR = 1.24 × 10−06 and “small GTPase mediated signal transduction” (FDR = 1.24 × 10−06. Genes up-regulated in AAA tissue showed a highly significant enrichment for GO categories “leukocyte migration” (FDR = 1.62 × 10−11, “activation of immune response” (FDR = 8.44 × 10−11, “T cell activation” (FDR = 4.14 × 10−10 and “regulation of lymphocyte activation” (FDR = 2.45 × 10−09, whereas the down-regulated genes were enriched in GO categories “cytoskeleton organization” (FDR = 7.84 × 10−05, “muscle cell development” (FDR = 1.00 × 10−04, and “organ morphogenesis” (FDR = 3.00 × 10−04. Quantitative PCR assays confirmed a sub-set of the transcription factor binding sites including those in MTMR11, DUSP10, ITGAM, MARCH1, HDAC8, MMP14, MAGI1, THBD and SPOCK1.

  19. Pathogen-mediated proteolysis of the cell death regulator RIPK1 and the host defense modulator RIPK2 in human aortic endothelial cells.

    Directory of Open Access Journals (Sweden)

    Andrés G Madrigal

    Full Text Available Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1, a mediator of tumor necrosis factor (TNF receptor-1 (TNF-R1-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1, NOD2, Toll-like receptor 2 (TLR2 or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose polymerase (PARP was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders.

  20. Pathogen-mediated proteolysis of the cell death regulator RIPK1 and the host defense modulator RIPK2 in human aortic endothelial cells.

    Science.gov (United States)

    Madrigal, Andrés G; Barth, Kenneth; Papadopoulos, George; Genco, Caroline Attardo

    2012-01-01

    Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC) has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1), a mediator of tumor necrosis factor (TNF) receptor-1 (TNF-R1)-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1), NOD2, Toll-like receptor 2 (TLR2) or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp) inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose) polymerase (PARP) was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders.

  1. Both common and specialty mushrooms inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells in a pro-inflammatory environment

    Directory of Open Access Journals (Sweden)

    Martin Keith R

    2010-07-01

    Full Text Available Abstract Background Cardiovascular disease (CVD is a leading cause of mortality in the United States as well as globally. Epidemiological studies show that regular fruit and vegetable consumption reduces CVD risk, in part, due to antioxidant activity and immunomodulation since oxidative stress and inflammation are features of atherogenesis. Accumulating evidence also shows that dietary fungi, viz., mushrooms, can protect against chronic disease by altering inflammatory environments such as those associated with CVD although most research has focused on specialty mushrooms. In this study, we tested the ability of both common and specialty mushrooms to inhibit cellular processes associated with CVD. Methods Human aortic endothelial cells (HAEC were incubated overnight with control media with dimethylsulfoxide (DMSO vehicle (1% v/v or containing DMSO extracts of whole dehydrated mushrooms (0.1 mg/mL, which included Agaricus bisporus (white button and crimini, Lentinula edodes (shiitake, Pleurotus ostreatus (oyster, and Grifola frondosa (maitake. Monolayers were subsequently washed and incubated with medium alone or containing the pro-inflammatory cytokine IL-1β (5 ng/mL for 6 h to upregulate pro-atherosclerotic adhesion molecules (AM. AM expression was assayed by ELISA and binding of U937 human monocytes pre-loaded with fluorescent dye was determined. Results White button mushrooms consistently reduced (p Conclusion These data provide evidence that dietary mushrooms can inhibit cellular processes such as adhesion molecule expression and ultimate binding of monocytes to the endothelium under pro-inflammatory conditions, which are associated with CVD. As a result, these findings support the notion that dietary mushrooms can be protective against CVD.

  2. Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Yao-Chang Chen

    2015-04-01

    Full Text Available Dihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroaustrasulfone alcohol has been shown to inhibit neointima formation, its effect on human vascular smooth muscle cells (VSMCs has not been elucidated. We examined the effects and the mechanisms of action of dihydroaustrasulfone alcohol on proliferation, migration and phenotypic modulation of human aortic smooth muscle cells (HASMCs. Dihydroaustrasulfone alcohol significantly inhibited proliferation, DNA synthesis and migration of HASMCs, without inducing cell death. Dihydroaustrasulfone alcohol also inhibited platelet-derived growth factor (PDGF-induced expression of cyclin-dependent kinases (CDK 2, CDK4, cyclin D1 and cyclin E. In addition, dihydroaustrasulfone alcohol inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2, whereas it had no effect on the phosphorylation of phosphatidylinositol 3-kinase (PI3K/(Akt. Moreover, treatment with PD98059, a highly selective ERK inhibitor, blocked PDGF-induced upregulation of cyclin D1 and cyclin E and downregulation of p27kip1. Furthermore, dihydroaustrasulfone alcohol also inhibits VSMC synthetic phenotype formation induced by PDGF. For in vivo studies, dihydroaustrasulfone alcohol decreased smooth muscle cell proliferation in a rat model of restenosis induced by balloon injury. Immunohistochemical staining showed that dihydroaustrasulfone alcohol noticeably decreased the expression of proliferating cell nuclear antigen (PCNA and altered VSMC phenotype from a synthetic to contractile state. Our findings provide important insights into the mechanisms underlying the vasoprotective actions of dihydroaustrasulfone alcohol and suggest that it may be a useful therapeutic agent

  3. The impact of scaled boundary conditions on wall shear stress computations in atherosclerotic human coronary bifurcations.

    Science.gov (United States)

    Schrauwen, Jelle T C; Schwarz, Janina C V; Wentzel, Jolanda J; van der Steen, Antonius F W; Siebes, Maria; Gijsen, Frank J H

    2016-05-15

    The aim of this study was to determine if reliable patient-specific wall shear stress (WSS) can be computed when diameter-based scaling laws are used to impose the boundary conditions for computational fluid dynamics. This study focused on mildly diseased human coronary bifurcations since they are predilection sites for atherosclerosis. Eight patients scheduled for percutaneous coronary intervention were imaged with angiography. The velocity proximal and distal of a bifurcation was acquired with intravascular Doppler measurements. These measurements were used for inflow and outflow boundary conditions for the first set of WSS computations. For the second set of computations, absolute inflow and outflow ratios were derived from geometry-based scaling laws based on angiography data. Normalized WSS maps per segment were obtained by dividing the absolute WSS by the mean WSS value. Absolute and normalized WSS maps from the measured-approach and the scaled-approach were compared. A reasonable agreement was found between the measured and scaled inflows, with a median difference of 0.08 ml/s [-0.01; 0.20]. The measured and the scaled outflow ratios showed a good agreement: 1.5 percentage points [-19.0; 4.5]. Absolute WSS maps were sensitive to the inflow and outflow variations, and relatively large differences between the two approaches were observed. For normalized WSS maps, the results for the two approaches were equivalent. This study showed that normalized WSS can be obtained from angiography data alone by applying diameter-based scaling laws to define the boundary conditions. Caution should be taken when absolute WSS is assessed from computations using scaled boundary conditions.

  4. Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

    Science.gov (United States)

    Chen, Dongquan; Stueckle, Todd A.; Luanpitpong, Sudjit; Rojanasakul, Yon; Lu, Yongju; Wang, Liying

    2015-01-01

    A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.

  5. Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

    National Research Council Canada - National Science Library

    Zeng, Qingchun; Song, Rui; Fullerton, David A; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B; Cleveland, Joseph C; Reece, T. Brett; McKinsey, Timothy A; Xu, Dingli; Dinarello, Charles A; Meng, Xianzhong

    2017-01-01

    ...) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation...

  6. Flow in an Aortic Coarctation

    Science.gov (United States)

    Loma, Luis; Miller, Paul; Hertzberg, Jean

    2009-11-01

    Coarctation of the aorta is a congenital cardiovascular defect that causes a constriction in the descending thoracic aorta. To gain a better understanding of the cause of post-surgical problems, a rigid glass and a compliant in vitro model of the aortic arch and descending aorta with a coarctation were constructed. Near-physiologic compliance was obtained using a silicone elastomer. Stereoscopic PIV was used to obtain 3D velocity maps. Results show a high speed turbulent jet formed at the exit of the coarctation. Flow in the rigid model was significantly different from in the compliant model. In the rigid model, the jet was symmetric, creating a toroidal recirculation area. In the compliant model, the jet was directed towards the medial wall, inducing flow reversal only at the lateral wall. Peak velocities and turbulence intensities were higher in the rigid model, however shear rate values in the compliant model were significantly above both the rigid model and normal in vivo values at the medial wall. In both models the reattachment region fluctuated, creating oscillatory shear.

  7. Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation.

    Science.gov (United States)

    Maiellaro-Rafferty, Kathryn; Weiss, Daiana; Joseph, Giji; Wan, William; Gleason, Rudolph L; Taylor, W Robert

    2011-08-01

    The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstructure during subclinical AAA development. We investigated the mechanisms of AAA in an angiotensin II (ANG II) infusion model of AAA in apolipoprotein E-deficient (apoE(-/-)) mice that overexpress catalase in vascular smooth muscle cells (apoE(-/-)xTg(SMC-Cat)). At baseline, aortas from apoE(-/-)xTg(SMC-Cat) exhibited increased stiffness and the microstructure was characterized by 50% more collagen content and less elastin fragmentation. ANG II treatment for 7 days in apoE(-/-) mice altered the transmural distribution of suprarenal aortic circumferential strain (quantified by opening angle, which increased from 130 ± 1° at baseline to 198 ± 8° after 7 days of ANG II treatment) without obvious changes in the aortic microstructure. No differences in aortic mechanical behavior or suprarenal opening angle were observed in apoE(-/-)xTg(SMC-Cat) after 7 days of ANG II treatment. These data suggest that at the earliest stages of AAA development H(2)O(2) is functionally important and is involved in the control of local variations in remodeling across the vessel wall. They further suggest that reduced elastin integrity at baseline may predispose the abdominal aorta to aneurysmal mechanical remodeling.

  8. Infolding of covered stents used for aortic coarctation: report of two cases.

    Science.gov (United States)

    Wan, Andrea W; Lee, Kyong-Jin; Benson, Lee N

    2014-01-01

    Covered stents have been used for the treatment of aortic coarctation to protect the arterial wall during dilation. Early results have shown them to be safe and effective. We report two cases of infolding of the proximal edge of a covered aortic coarctation stent. Management required implantation of a second stent. Poor stent apposition to the vessel wall and/or recoil may allow conditions for these events to occur.

  9. Asymptomatic papillary fibroelastoma of the Aortic valve in a young woman - a case report

    Directory of Open Access Journals (Sweden)

    Pitsis Antonis

    2009-09-01

    Full Text Available Abstract Echocardiography represents an invaluable diagnostic tool for the detection of intracardiac masses while simultaneously provides information about their size, location, mobility and attachment site as well as the presence and extent of any consequent hemodynamic derangement. A 29-year-old asymptomatic young woman with incidental transthoracic echocardiographic (TTE discovery of an aortic valve mass is presented. The 2-dimensional TTE showed a mobile, pedunculated mass, attached by a thin stalk to the aortic surface of the right coronary aortic cusp at the junction of its base with the anterior aortic wall. The importance of valve sparing tumour resection even in asymptomatic patients is emphasised.

  10. No renal phenotype in human phospholipid transfer protein transgenic apolipoprotein E deficient mice despite severe aortic atherosclerosis

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van Haperen, Rien; van den Born, Jaap; van Goor, Harry; de Crom, Rini; van Tol, Arie

    2014-01-01

    Background: Phospholipid transfer protein (PLTP) is an emerging cardiometabolic risk factor. Plasma PLTP is elevated in humans with end-stage kidney disease and glomerular proteinuria, but the contribution of systemic PLTP elevation to the development of renal damage is unknown. We tested whether hu

  11. Aortic Valve Stenosis

    Science.gov (United States)

    ... evaluation of aortic stenosis in adults. http://www.uptodate.com/home. Accessed April 29, 2014. Mohty D, ... Valvular heart disease in elderly adults. http://www.uptodate.com/home. Accessed May 2, 2014. Bonow RO, ...

  12. Bicuspid aortic valve

    Science.gov (United States)

    ... aortic disease. In: Otto CM, Bonow RO, eds. Valvular Heart Disease: A Companion to Braunwald's Heart Disease . 4th ed. ... PA: Elsevier Saunders; 2014:chap 13. Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  13. Aortic Valve Regurgitation

    Science.gov (United States)

    ... inside your heart that involves heart valves. Rheumatic fever. Rheumatic fever — a complication of strep throat and once a ... the United States — can damage the aortic valve. Rheumatic fever is still prevalent in developing countries but rare ...

  14. Nonsteroidal antiinflammatory drugs are associated with increased aortic stiffness

    Directory of Open Access Journals (Sweden)

    Martin Claridge

    2005-07-01

    Full Text Available Martin Claridge1, Simon Hobbs1, Clive Quick2, Nick Day3, Andrew Bradbury1, Teun Wilmink11Department of Vascular Surgery, University of Birmingham, Birmingham Heartlands Hospital Birmingham, UK; 2Department of Surgery, Hinchingbrooke Hospital, Huntingdon, UK; 3Department of Epidemiology and Biostatistics, University of Cambridge, Cambridge, UKObjectives: Nonsteroidal antiinflammatory drugs (NSAIDS have been shown to retard aneurysm growth in animal models. In vitro studies have shown an inhibitory effect of NSAIDS on matrix metalloproteinase-9, interleukin-1β, and IL-6 mediated arterial wall elastolysis. The aim of this study was to investigate the effects of NSAIDs on arterial stiffness, a surrogate marker of elastolysis.Methods: 447 subjects enrolled in a community-based abdominal aortic aneurysm (AAA screening program were assessed for age, blood pressure, smoking status, and drug history. Aortic diameter and stiffness were measured by M-Mode ultrasound. The concentration of the amino-terminal propeptide of type III procollagen was used as a proxy measurement of type III collagen turnover.Results: NSAID ingestion was significantly (p = 0.006 associated with increased aortic wall stiffness after adjusting for age, aortic diameter, blood pressure, and smoking status. No such effect was seen for β-blockers, calcium channel antagonists, nitrates, angiotensin-converting enzyme inhibitors, diuretics, or antiplatelet agents.Discussion: These novel data show that NSAIDS are associated with increased aortic stiffness, possibly through the effects of cytokine mediated elastolysis. This in turn may prevent aortic expansion and the development of AAA.Keywords: nonsteroidal antiinflammatory drugs, abdominal aortic aneurysm, aortic stiffness, elastolysis

  15. Fatal Saccharomyces Cerevisiae Aortic Graft Infection

    Science.gov (United States)

    Meyer, Michael (Technical Monitor); Smith, Davey; Metzgar, David; Wills, Christopher; Fierer, Joshua

    2002-01-01

    Saccharomyces cerevisiae is a yeast commonly used in baking and a frequent colonizer of human mucosal surfaces. It is considered relatively nonpathogenic in immunocompetent adults. We present a case of S. cerevisiae fungemia and aortic graft infection in an immunocompetent adult. This is the first reported case of S. cerevisiue fungemia where the identity of the pathogen was confirmed by rRNA sequencing.

  16. Anti-atherogenic effect of trivalent chromium-loaded CPMV nanoparticles in human aortic smooth muscle cells under hyperglycemic conditions in vitro

    Science.gov (United States)

    Ganguly, Rituparna; Wen, Amy M.; Myer, Ashley B.; Czech, Tori; Sahu, Soumyadip; Steinmetz, Nicole F.; Raman, Priya

    2016-03-01

    Atherosclerosis, a major macrovascular complication associated with diabetes, poses a tremendous burden on national health care expenditure. Despite extensive efforts, cost-effective remedies are unknown. Therapies for atherosclerosis are challenged by a lack of targeted drug delivery approaches. Toward this goal, we turn to a biology-derived drug delivery system utilizing nanoparticles formed by the plant virus, Cowpea mosaic virus (CPMV). The aim herein is to investigate the anti-atherogenic potential of the beneficial mineral nutrient, trivalent chromium, loaded CPMV nanoparticles in human aortic smooth muscle cells (HASMC) under hyperglycemic conditions. A non-covalent loading protocol is established yielding CrCl3-loaded CPMV (CPMV-Cr) carrying 2000 drug molecules per particle. Using immunofluorescence microscopy, we show that CPMV-Cr is readily taken up by HASMC in vitro. In glucose (25 mM)-stimulated cells, 100 nM CPMV-Cr inhibits HASMC proliferation concomitant to attenuated proliferating cell nuclear antigen (PCNA, proliferation marker) expression. This is accompanied by attenuation in high glucose-induced phospho-p38 and pAkt expression. Moreover, CPMV-Cr inhibits the expression of pro-inflammatory cytokines, transforming growth factor-β (TGF-β) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), in glucose-stimulated HASMCs. Finally glucose-stimulated lipid uptake is remarkably abrogated by CPMV-Cr, revealed by Oil Red O staining. Together, these data provide key cellular evidence for an atheroprotective effect of CPMV-Cr in vascular smooth muscle cells (VSMC) under hyperglycemic conditions that may promote novel therapeutic ventures for diabetic atherosclerosis.

  17. Shear stress induces human aortic endothelial cell apoptosis via interleukin‑1 receptor‑associated kinase 2‑induced endoplasmic reticulum stress.

    Science.gov (United States)

    Pan, Longfei; Hong, Zhou; Yu, Lei; Gao, Yanxia; Zhang, Rui; Feng, Hui; Su, Lijuan; Wang, Gang

    2017-09-19

    Atherosclerosis is characterized by localized lesions distributed in the arterial tree due to the shear stress produced by blood flow. Endothelial cells are directly affected by alterations in blood flow. Dysfunction and injury to endothelial cells has been hypothesized to initiate the pathological processes of atherosclerosis. The present study aimed to investigate the mechanism of shear stress‑induced endothelial cellular apoptosis. Shear stress was generated using an artificial device to mimic the impact of disturbed blood flow on cultured human aortic endothelial cells (HAECs). Cellular apoptosis was assessed using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay; an ELISA assay was used to detect the produced interleukin (IL)‑1β; specific small interfering (si)RNA was used to knockdown the expression of interleukin‑1 receptor‑associated kinase 2 (IRAK2) in HAECs and the expression levels of 78 kDa glucose‑regulated protein, DNA damage‑inducible transcript 3 protein (CHOP), IRAK2 and IL‑1β were evaluated using western blotting. The results of the present study demonstrated that artificial shear stress induced endoplasmic reticulum (ER) stress, IL‑1β production and apoptosis in HAECs in a time‑dependent manner. The inhibition of ER stress, and treatment with interleukin‑1 receptor antagonist protein and siRNA against IRAK2 attenuated shear stress‑induced CHOP signaling‑mediated cellular apoptosis. Therefore, overproduction of IL‑1β exacerbated shear stress‑induced ER stress‑mediated apoptosis via the IRAK2/CHOP signaling pathway in endothelial cells.

  18. Human aortic fibrolipid lesions. Progenitor lesions for fibrous plaques, exhibiting early formation of the cholesterol-rich core.

    OpenAIRE

    Bocan, T. M.; Guyton, J. R.

    1985-01-01

    The early development of the lipid-rich core and other features of atherosclerotic fibrous plaques has been elucidated by examining discrete, small regions of raised intima in human aorta, which often bear a resemblance to both fatty streaks and fibrous plaques. Approximately one-fourth of small raised lesions (less than 16 sq mm of surface area) contained little or no stainable lipid, while three-fourths had a characteristic appearance, which included a superficial layer of foam cells, a cor...

  19. Human aortic fibrolipid lesions. Progenitor lesions for fibrous plaques, exhibiting early formation of the cholesterol-rich core.

    OpenAIRE

    Bocan, T. M.; Guyton, J. R.

    1985-01-01

    The early development of the lipid-rich core and other features of atherosclerotic fibrous plaques has been elucidated by examining discrete, small regions of raised intima in human aorta, which often bear a resemblance to both fatty streaks and fibrous plaques. Approximately one-fourth of small raised lesions (less than 16 sq mm of surface area) contained little or no stainable lipid, while three-fourths had a characteristic appearance, which included a superficial layer of foam cells, a cor...

  20. Spontaneous retrograde dissection of the ascending aorta in a patient with a bicuspid aortic valve.

    Science.gov (United States)

    Akgullu, Cagdas; Hekim, Tolga; Eryilmaz, Ufuk; Kurtoğlu, Tünay; Gürcün, Uğur

    2013-06-23

    Bicuspid aortic valve (BAV) is a congenital anomaly associated with structural weakness of the aortic wall. Sudden onset of symptoms in patients with BAV, such as sudden severe back pain, and pulse inequality between the extremities or tension disparity should alert clinicians to acute aortic syndromes, as they require prompt diagnosis and management. Retrograde aortic dissection, which is a rare form of acute aortic syndrome, is an uncommon life-threatening entity and may produce atypical computed tomography (CT) or magnetic resonance imaging findings, leading to difficulty in diagnosis. We report on a 51-year-old male patient with BAV and spontaneous retrograde ascending aortic dissection. CT findings were confusing and the diagnosis was made via transoesophageal echocardiography. After the diagnosis, the patient was treated with a modified Bentall procedure. He did not have any complications and was stable four months after the operation.

  1. Aortic and mitral valve surgery on the beating heart is lowering cardiopulmonary bypass and aortic cross clamp time.

    Science.gov (United States)

    Gersak, Borut; Sutlic, Zeljko

    2002-01-01

    the selected high risk patients or to minimize the deleterious effects of cardiopulmonary bypass (CPB) on the overall postoperative performance [Calafiore 1996, Tasdemir 1998]. Due to the fact, that the cardiac muscle should be protected at most during the cardiac arrest, retrograde blood cardioplegia was successfully introduced [Buckberg 1990], and more - the warm cardioplegia is being used recently [Kawasuji 1997]. The natural status of the human heart is the beating status, so it is reasonable to try to perform the operations on the beating heart. This has been done recently with the MID - CAB and OP - CAB (off-pump CABG) operations [Tasdemir 1998]. The retrograde warm blood cardioplegia has therefore led us to the premise, that with retrograde oxygenated blood perfusion it would be possible to achieve the operations on the beating heart even in the open heart surgery, such as aortic and/or mitral valve surgery. All will agree that the most damaging effect of the cardioplegia is the reperfusion injury [Allen 1997], and it is obvious that with the technique of retrograde continuous oxygenated blood perfusion this effect will be canceled. In this article, we would like to show the how-to technique for the operations on the beating heart in the case of operations on the aortic valve replacement (AVR) with mitral valve repair (MVR) or replacement MVR and with/without concomitant coronary artery bypass (CABG) surgery. The tricuspid valve repair (PTV) is normally done on the beating heart and there it is realized what problems or technical difficulties may arise during procedures on the mitral valve: the walls of the ventricles are not flattened and the exposure of the mitral valve is challenging task. Furthermore, the free walls of the ventricles with interventricular septum are in the state of the tonus, so every force applied to better expose the aortic or mitral valve is not acceptable

  2. Textural Feature Selection for Enhanced Detection of Stationary Humans in Through the Wall Radar Imagery

    Science.gov (United States)

    2014-05-02

    b) (c) Figure 2. (a) Through-the-wall MIMO System. (b) Building used for Through-the-Wall Measurements (the dashed square indicates the...number of training samples at the parent node t and iQ is the number of training samples associated with the child node iv . The Gini index is a...also be determined by using the weighted average of the Gini index. The training samples are first sorted based on the values they take for the feature

  3. Abdominal aortic aneurysms : clinical insights and outcome after endovascular repair

    NARCIS (Netherlands)

    Zandvoort, H.J.A.

    2013-01-01

    Abdominal aortic aneurysm (AAA) is a focal dilatation of the abdominal aorta. The pathophysiology of AAA is a complex multifactorial process and much is still unknown. Histologic and biochemical analysis of AAA wall characteristics can contribute to a better insight in AAA pathophysiology. To make t

  4. Jet length/velocity ratio: a new index for echocardiographic evaluation of chronic aortic regurgitation.

    Science.gov (United States)

    Güvenç, Tolga Sinan; Karaçimen, Denizhan; Erer, Hatice Betül; İlhan, Erkan; Sayar, Nurten; Karakuş, Gültekin; Çekirdekçi, Elif; Eren, Mehmet

    2015-01-01

    Management of aortic regurgitation depends on the assessment for severity. Echocardiography remains as the most widely available tool for evaluation of aortic regurgitation. In this manuscript, we describe a novel parameter, jet length/velocity ratio, for the diagnosis of severe aortic regurgitation. A total of 30 patients with aortic regurgitation were included to this study. Severity of aortic regurgitation was assessed with an aortic regurgitation index incorporating five echocardiographic parameters. Jet length/velocity ratio is calculated as the ratio of maximum jet penetrance to mean velocity of regurgitant flow. Jet length/velocity ratio was significantly higher in patients with severe aortic regurgitation (2.03 ± 0.53) compared to patients with less than severe aortic regurgitation (1.24 ± 0.32, P < 0.001). Correlation of jet length/velocity ratio with aortic regurgitation index was very good (r(2) = 0.86) and correlation coefficient was higher for jet length/velocity ratio compared to vena contracta, jet width/LVOT ratio and pressure half time. For a cutoff value of 1.61, jet length/velocity ratio had a sensitivity of 92% and specificity of 88%, with an AUC value of 0.955. Jet length/velocity ratio is a novel parameter that can be used to assess severity of chronic aortic regurgitation. Main limitation for usage of this novel parameter is jet impringement to left ventricular wall. © 2014, Wiley Periodicals, Inc.

  5. Pulmonary vein and atrial wall pathology in human total anomalous pulmonary venous connection

    NARCIS (Netherlands)

    Douglas, Yvonne L.; Jongbloed, Monique R. M.; den Hartog, Wietske C. E.; Bartelings, Margot M.; Bogers, Ad J. J. C.; Ebels, Tjark; DeRuiter, Marco C.; Gittenberger-de Groot, Adriana C.

    2009-01-01

    Background: Normally, the inside of the left atrial (LA) body and pulmonary veins (PVs) is lined by vessel wall tissue covered by myocardium. In total anomalous pulmonary venous connection (TAPVC), no connection of the PVs with the LA body exists. These veins have an increased incidence of PV

  6. Reconstruction of the abdominal wall by using a combination of the human acellular dermal matrix implant and an interpositional omentum flap after extensive tumor resection in patients with abdominal wall neoplasm:A preliminary result

    Institute of Scientific and Technical Information of China (English)

    Yan Gu; Rui Tang; Ding-Quan Gong; Yun-Liang Qian

    2008-01-01

    AIM:To present our trial using a combination of the human acellular dermal matrix (HADM) implant and an interpositional omentum flap to repair giant abdominal wall defects after extensive tumor resection.METHODS:Between February and October of 2007,three patients with giant defects of the abdominal wall after extensive tumor resection underwent reconstruction with a combination of HADM and omentum flap.Postoperative morbidities and signs of herniation were monitored.RESULTS:The abdominal wall reconstruction was successful in these three patients,there was no severe morbidity and no signs of herniation in the follow-up period.CONCLUSION:The combination of HADM and omentum flap offers a new,safe and effective alternative to traditional forms in the repair of giant abdominal wall defects.Further analysis of the long-term outcome and more cases are needed to assess the reliability of this technique.

  7. Screening for Abdominal Aortic Aneurysm

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Abdominal Aortic Aneurysm The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Abdominal Aortic Aneurysm. This final ...

  8. Abdominal aortic aneurysm repair - open

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007392.htm Abdominal aortic aneurysm repair - open To use the sharing features on this page, please enable JavaScript. Open abdominal aortic aneurysm repair is surgery to fix a widened part ...

  9. Hemodynamic predictors of aortic dilatation in bicuspid aortic valve by velocity-encoded cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Ramamurthy Senthil

    2010-01-01

    Full Text Available Abstract Background Congenital Bicuspid Aortic Valve (BAV is a significant risk factor for serious complications including valve dysfunction, aortic dilatation, dissection, and sudden death. Clinical tools for identification and monitoring of BAV patients at high risk for development of aortic dilatation, an early complication, are not available. Methods This paper reports an investigation in 18 pediatric BAV patients and 10 normal controls of links between abnormal blood flow patterns in the ascending aorta and aortic dilatation using velocity-encoded cardiovascular magnetic resonance. Blood flow patterns were quantitatively expressed in the angle between systolic left ventricular outflow and the aortic root channel axis, and also correlated with known biochemical markers of vessel wall disease. Results The data confirm larger ascending aortas in BAV patients than in controls, and show more angled LV outflow in BAV (17.54 ± 0.87 degrees than controls (10.01 ± 1.29 (p = 0.01. Significant correlation of systolic LV outflow jet angles with dilatation was found at different levels of the aorta in BAV patients STJ: r = 0.386 (N = 18, p = 0.048, AAO: r = 0.536 (N = 18, p = 0.022, and stronger correlation was found with patients and controls combined into one population: SOV: r = 0.405 (N = 28, p = 0.033, STJ: r = 0.562 (N = 28, p = 0.002, and AAO r = 0.645 (N = 28, p Conclusions The results of this study provide new insights into the pathophysiological processes underlying aortic dilatation in BAV patients. These results show a possible path towards the development of clinical risk stratification protocols in order to reduce morbidity and mortality for this common congenital heart defect.

  10. [Congenital aortic stenosis].

    Science.gov (United States)

    Yamaguchi, M

    2001-08-01

    Recent advances in and controversies concerning the management of children with congenital valvular aortic stenosis are discussed. In neonates with critical aortic stenosis, improved survival has recently been reported after surgical open valvotomy and balloon valvuloplasty, although it is difficult at this point to compare the results of the two procedures and determine their differential indications. Good results have also been achieved after extended aortic valvuloplasty for recurrent aortic stenosis and/or insufficiency, but the length of follow-up in these patients is still short. The technique first reported in 1991 for bilateral enlargement fo a small annulus permits the insertion of an aortic valve 3-4 sizes larger than the native annulus. It entails no risk of distorting the mitral valve, damaging the conduction system or important branches of the coronary arteries, or resulting in left ventricular dysfunction. The Ross procedure is now widely applied in the West, with reports of early mortality rates of less than 5% and event-free survival rates of 80-90% during follow-up of 4-8 years. Longer follow-up and continued careful evaluation are required to resolve the issue of possible dilatation and subsequent neoaortic valve dysfunction and pulmonary stenosis due to allograft degeneration after pulmonary autograft root replacement in children.

  11. AGE/RAGE promotes thecalcification of human aortic smooth muscle cells via the Wnt/β-catenin axis.

    Science.gov (United States)

    Liu, Yong; Wang, Wei-Ming; Zhang, Xue-Lin; He, Hu-Qiang; Sun, Xiao-Lei; Zeng, Hong; Xu, Xiong-Fei; Huang, Liang; Zhu, Zhi; Zhang, Lei; Zhou, Xiang-Yu; He, Yan-Zheng

    2016-01-01

    The present study aims to investigate whether RAGE promotes the calcification of human arterial smooth muscle cells (HASMCs) and determine the relationshipbetween RAGE and the Wnt/β-catenin signaling pathway in this process. In this study,there were four groups, namelythe blank control group, the non-transfection group, the empty vector group, and the RAGE transfection group.Cells were co-cultured with 10 mmol/L β-glycerophosphoric acid, pyruvate and 20 mg/L AGE. The expression of osteogenic proteins in each group before and after the intervention wasdetected using Western blotting. Short interfering RNA (siRNA) targeting β-catenin was used toinhibitthe expression of β-catenin. HASMCs cultured under normal conditions were usedas the blank control. (1) High RAGE expression was successfully induced in HASMCs according to the results of GFP detection, flow cytometry and Western blotting. (2) Compared with the blank control group, non-transfection group and empty vector group, RAGE transfection enhanced the calcification of cells when incubated with calcification medium plus AGE. (3) The expression of RAGE, β-catenin, OPG and Cbfa1 proteins in the blank control group, empty vector group and RAGE transfection group wasnot significantly enhanced after intervention. However, expression of the proteins in the RAGE transfection group was much higher than those of the other groups. (4) Compared with the RAGE transfection group and control siRNA group, the cells transfected with β-catenin siRNA and cultured with interventional drugs showed significant inhibition of the expression of the downstream Cbfa1 and OPG genes. Increased expression of RAGE promoted calcification in HASMCs and up regulated the β-catenin, OPG and Cbfa1 genes. RAGE may activate the downstream genes via the Wntβ-catenin pathway, thereby promoting HASMC differentiation into osteogenic cells and calcification.

  12. Human aortic fibrolipid lesions. Progenitor lesions for fibrous plaques, exhibiting early formation of the cholesterol-rich core.

    Science.gov (United States)

    Bocan, T. M.; Guyton, J. R.

    1985-01-01

    The early development of the lipid-rich core and other features of atherosclerotic fibrous plaques has been elucidated by examining discrete, small regions of raised intima in human aorta, which often bear a resemblance to both fatty streaks and fibrous plaques. Approximately one-fourth of small raised lesions (less than 16 sq mm of surface area) contained little or no stainable lipid, while three-fourths had a characteristic appearance, which included a superficial layer of foam cells, a core of noncrystalline and/or crystalline lipid, and a developed or developing collagenous cap. Total intimal volumes of the lipid-containing lesions, termed "fibrolipid lesions," ranged from 3 to 43 microliters, with the majority less than 16 microliters. Core lipid in the smallest lesions was located in the musculoelastic layer of the intima. In larger lesions the core extended luminally into the elastic hyperplastic layer, and cholesterol crystals were found more frequently. Total cholesterol concentration in fibrolipid lesions was similar to that in fatty streaks; however, the ratio of unesterified to total cholesterol was relatively high, similar to that found in fibrous plaques. It is concluded that 1) the formation of a lipid-rich core and cholesterol crystallization are early events in the development of many raised lesions; 2) the consistent association between the superficial layer of foam cells and the deep-lying lipid-rich core raises the possibility of an influence, possibly indirect, of foam-cell lipid metabolism on core formation; and 3) the fibrolipid lesion may represent one stage in a potential transitional morphologic sequence between fatty streak and fibrous plaque. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:4025509

  13. Isolate-dependent growth, virulence, and cell wall composition in the human pathogen Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Nansalmaa Amarsaikhan

    Full Text Available The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.

  14. Mechanism of synchronized change in ultrasonic integrated backscatter across human heart wall

    Science.gov (United States)

    Tobinai, Yumi; Taki, Hirofumi; Kanai, Hiroshi

    2017-07-01

    Ultrasonic integrated backscatter (IB) from the heart wall, which has been employed for quantitative tissue characterization of the myocardium, is known to have cyclic variation-a decrease in systole and an increase in diastole. In the present study, by tracking the measurement position of the myocardium and compensating for the movement due to the heartbeat, IB and its temporal variation were obtained from the same site with a high temporal resolution of 1.73 ms. In an in vivo study on a healthy subject, the temporal variation of IB values homogeneously changed across the heart wall, especially during the slow filling and the atrial systole phases. This new finding shows that the IB value reflects a small movement of the myocardium of about 5 mm/s. Thus, the proposed measurement has a potential for quantitative and accurate evaluation of the contraction and relaxation of the myocardium.

  15. Anatomic distribution of nerves and microvascular density in the human anterior vaginal wall: prospective study.

    Directory of Open Access Journals (Sweden)

    Ting Li

    Full Text Available BACKGROUND: The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina remains controversial. We explored the histomorphological basis of the G-spot. METHODS: Biopsies were drawn from a 12 o'clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5-immunoreactive nerves and smooth muscle actin-immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. RESULTS: Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000 and in the vaginal muscle layer (p = 0.006. There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046 and muscle layer (p = 0.002. CONCLUSIONS: Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction.

  16. Paradoxical adverse culture conditions do not hamper the growth of human multipotent vascular wall-mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Carmen eCiavarella

    2015-06-01

    Full Text Available Background: Mesenchymal stem cells (MSCs with multilineage potential and anti-inflammatory property can be isolated from different human tissues, representing promising candidates in regenerative medicine. Despite the common criteria of characterization, many factors contribute to MSC heterogeneity (i.e. tissue origin, coexistence of cell subsets at different stage of differentiation, epigenetic and no standard methods have been approved to characterize MSCs in cell culture.Aim: The present study aimed to test whether MSCs resist adverse chemical and physical culture conditions, surviving MSC subpopulations are endowed with the stemness abilities; to characterize MMP expression in AAA-MSCs under the adverse experimental conditions. Methods and results: MSCs enzymatically isolated from human abdominal aortic aneurysm (AAA-MSCs were exposed to media acidification, hypoxia, starving, drying and hypothermia through the following strategies: 1 low-density seeding in closed flasks; 2 exposure to a chemical hypoxia inducer, cobalt chloride; 3 exposure to a dry environment with growing medium deprivation and culture at 4°C. None of these conditions affected MSC viability and stemness profile, as evidenced by NANOG, OCT-4 and Sox-2 mRNA expression in surviving cells. A significant MMP-9 decrease, especially when AAA-MSCs were exposed to hypothermia, was associated with stress resistant stem cells.Conclusions: AAA-MSCs survive to extremely adverse culture conditions, keeping their morphology and stemness features. Besides MMP-9 role in pathological tissue remodeling, this protease may be related to MSC survival. Future studies on MSCs derived from other tissues will be necessary to refine our culture protocol, which can represent an empirical method to demonstrate MSC stemness,, with potential implications for their clinical use.

  17. The spatial arrangement of the human large intestinal wall blood circulation

    Science.gov (United States)

    Kachlik, David; Baca, Vaclav; Stingl, Josef

    2010-01-01

    The aim of the study was to describe and depict the spatial arrangement of the colon microcirculatory bed as a whole. Various parts of the large intestine and terminal ileum were harvested from either cadaver or section material or gained peroperatively. Samples were then injected with India ink or methylmetacrylate Mercox resin for microdissection and corrosion casting for scanning electron microscopy. The results showed that extramural vasa recta ramified to form the subserous plexus, some of them passing underneath the colon taeniae. Branches of both short and long vasa recta merged in the colon wall, pierced the muscular layer and spread out as the submucous plexus, which extended throughout the whole intestine without any interruption. The muscular layer received blood via both the centrifugal branches of the submucous plexus and the minor branches sent off by the subserous plexus. The mucosa was supplied by the mucous plexus, which sent capillaries into the walls of intestinal glands. The hexagonal arrangement of the intestinal glands reflected their vascular bed. All three presumptive critical points are only gross anatomical points of no physiological relevance in healthy individuals. Neither microscopic weak points nor regional differences were proven within the wall of the whole large intestine. The corrosion casts showed a huge density of capillaries under the mucosa of the large intestine. A regular hexagonal pattern of the vascular bed on the inner surface was revealed. No microvascular critical point proofs were confirmed and a correlation model to various pathological states was created. PMID:20447248

  18. Through Wall Radar Classification of Human Micro-Doppler Using Singular Value Decomposition Analysis.

    Science.gov (United States)

    Ritchie, Matthew; Ash, Matthew; Chen, Qingchao; Chetty, Kevin

    2016-08-31

    The ability to detect the presence as well as classify the activities of individuals behind visually obscuring structures is of significant benefit to police, security and emergency services in many situations. This paper presents the analysis from a series of experimental results generated using a through-the-wall (TTW) Frequency Modulated Continuous Wave (FMCW) C-Band radar system named Soprano. The objective of this analysis was to classify whether an individual was carrying an item in both hands or not using micro-Doppler information from a FMCW sensor. The radar was deployed at a standoff distance, of approximately 0.5 m, outside a residential building and used to detect multiple people walking within a room. Through the application of digital filtering, it was shown that significant suppression of the primary wall reflection is possible, significantly enhancing the target signal to clutter ratio. Singular Value Decomposition (SVD) signal processing techniques were then applied to the micro-Doppler signatures from different individuals. Features from the SVD information have been used to classify whether the person was carrying an item or walking free handed. Excellent performance of the classifier was achieved in this challenging scenario with accuracies up to 94%, suggesting that future through wall radar sensors may have the ability to reliably recognize many different types of activities in TTW scenarios using these techniques.

  19. Through Wall Radar Classification of Human Micro-Doppler Using Singular Value Decomposition Analysis

    Directory of Open Access Journals (Sweden)

    Matthew Ritchie

    2016-08-01

    Full Text Available The ability to detect the presence as well as classify the activities of individuals behind visually obscuring structures is of significant benefit to police, security and emergency services in many situations. This paper presents the analysis from a series of experimental results generated using a through-the-wall (TTW Frequency Modulated Continuous Wave (FMCW C-Band radar system named Soprano. The objective of this analysis was to classify whether an individual was carrying an item in both hands or not using micro-Doppler information from a FMCW sensor. The radar was deployed at a standoff distance, of approximately 0.5 m, outside a residential building and used to detect multiple people walking within a room. Through the application of digital filtering, it was shown that significant suppression of the primary wall reflection is possible, significantly enhancing the target signal to clutter ratio. Singular Value Decomposition (SVD signal processing techniques were then applied to the micro-Doppler signatures from different individuals. Features from the SVD information have been used to classify whether the person was carrying an item or walking free handed. Excellent performance of the classifier was achieved in this challenging scenario with accuracies up to 94%, suggesting that future through wall radar sensors may have the ability to reliably recognize many different types of activities in TTW scenarios using these techniques.

  20. The spatial arrangement of the human large intestinal wall blood circulation.

    Science.gov (United States)

    Kachlik, David; Baca, Vaclav; Stingl, Josef

    2010-03-01

    The aim of the study was to describe and depict the spatial arrangement of the colon microcirculatory bed as a whole. Various parts of the large intestine and terminal ileum were harvested from either cadaver or section material or gained peroperatively. Samples were then injected with India ink or methylmetacrylate Mercox resin for microdissection and corrosion casting for scanning electron microscopy. The results showed that extramural vasa recta ramified to form the subserous plexus, some of them passing underneath the colon taeniae. Branches of both short and long vasa recta merged in the colon wall, pierced the muscular layer and spread out as the submucous plexus, which extended throughout the whole intestine without any interruption. The muscular layer received blood via both the centrifugal branches of the submucous plexus and the minor branches sent off by the subserous plexus. The mucosa was supplied by the mucous plexus, which sent capillaries into the walls of intestinal glands. The hexagonal arrangement of the intestinal glands reflected their vascular bed. All three presumptive critical points are only gross anatomical points of no physiological relevance in healthy individuals. Neither microscopic weak points nor regional differences were proven within the wall of the whole large intestine. The corrosion casts showed a huge density of capillaries under the mucosa of the large intestine. A regular hexagonal pattern of the vascular bed on the inner surface was revealed. No microvascular critical point proofs were confirmed and a correlation model to various pathological states was created.

  1. Aortic Wave Dynamics and Its Influence on Left Ventricular Workload

    Science.gov (United States)

    Pahlevan, Niema; Gharib, Morteza

    2010-11-01

    Clinical and epidemiologic studies have shown that hypertension plays a key role in development of left ventricular (LV) hypertrophy and ultimately heart failure mostly due to increased LV workload. Therefore, it is crucial to diagnose and treat abnormal high LV workload at early stages. The pumping mechanism of the heart is pulsatile, thus it sends pressure and flow wave into the compliant aorta. The wave dynamics in the aorta is dominated by interplay of heart rate (HR), aortic rigidity, and location of reflection sites. We hypothesized that for a fixed cardiac output (CO) and peripheral resistance (PR), interplay of HR and aortic compliance can create conditions that minimize LV power requirement. We used a computational approach to test our hypothesis. Finite element method with direct coupling method of fluid-structure interaction (FSI) was used. Blood was assumed to be incompressible Newtonian fluid and aortic wall was considered elastic isotropic. Simulations were performed for various heart rates and aortic rigidities while inflow wave, CO, and PR were kept constant. For any aortic compliance, LV power requirement becomes minimal at a specific heart rate. The minimum shifts to higher heart rates as aortic rigidity increases.

  2. Pulsatile blood flow in Abdominal Aortic Aneurysms

    Science.gov (United States)

    Salsac, Anne-Virginie; Lasheras, Juan C.; Singel, Soeren; Varga, Chris

    2001-11-01

    We discuss the results of combined in-vitro laboratory measurements and clinical observations aimed at determining the effect that the unsteady wall shear stresses and the pressure may have on the growth and eventual rupturing of an Abdominal Aortic Aneurysm (AAA), a permanent bulging-like dilatation occurring near the aortic bifurcation. In recent years, new non-invasive techniques, such as stenting, have been used to treat these AAAs. However, the development of these implants, aimed at stopping the growth of the aneurysm, has been hampered by the lack of understanding of the effect that the hemodynamic forces have on the growth mechanism. Since current in-vivo measuring techniques lack the precision and the necessary resolution, we have performed measurements of the pressure and shear stresses in laboratory models. The models of the AAA were obtained from high resolution three-dimensional CAT/SCANS performed in patients at early stages of the disease. Preliminary DPIV measurements show that the pulsatile blood flow discharging into the cavity of the aneurysm leads to large spikes of pressure and wall shear stresses near and around its distal end, indicating a possible correlation between the regions of high wall shear stresses and the observed location of the growth of the aneurysm.

  3. Robotic aortic surgery.

    Science.gov (United States)

    Duran, Cassidy; Kashef, Elika; El-Sayed, Hosam F; Bismuth, Jean

    2011-01-01

    Surgical robotics was first utilized to facilitate neurosurgical biopsies in 1985, and it has since found application in orthopedics, urology, gynecology, and cardiothoracic, general, and vascular surgery. Surgical assistance systems provide intelligent, versatile tools that augment the physician's ability to treat patients by eliminating hand tremor and enabling dexterous operation inside the patient's body. Surgical robotics systems have enabled surgeons to treat otherwise untreatable conditions while also reducing morbidity and error rates, shortening operative times, reducing radiation exposure, and improving overall workflow. These capabilities have begun to be realized in two important realms of aortic vascular surgery, namely, flexible robotics for exclusion of complex aortic aneurysms using branched endografts, and robot-assisted laparoscopic aortic surgery for occlusive and aneurysmal disease.

  4. Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

    Science.gov (United States)

    Scordo, Julia M.; Arcos, Jesús; Kelley, Holden V.; Diangelo, Lauren; Sasindran, Smitha J.; Youngmin, Ellie; Wewers, Mark D.; Wang, Shu-Hua; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B.

    2017-01-01

    In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis (M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site. PMID:28373877

  5. Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1.

    Science.gov (United States)

    Wu, Zhiyong; Dai, Feifeng; Ren, Wei; Liu, Huagang; Li, Bowen; Chang, Jinxing

    2016-01-01

    Patients with acute aortic dissection (AAD) usually showed acute lung injury (ALI). However, its pathogenesis is still not well defined. Apoptosis of pulmonary microvascular endothelial cells (PMVECs) is closely related to the alveolus-capillary barrier injury and the increased vascular permeability. In this study, we aim to investigate the human PMVECs (hPMVECs) apoptosis induced by angiotensin II (AngII) and monocyte chemoattractant protein-1 (MCP-1) and their potential interaction in the pathogenesis of AAD complicated with ALI. Fifty-eight newly diagnosed AAD, 12 matched healthy individuals were included. Pulmonary tissues of AAD complicated with lung injury were obtained from 2 cadavers to determine the levels of AngII type 1 receptor (AT1-R) and MCP-1. Serum AngII was measured using commercial ELISA kit. H&E staining and immunohistostaining were performed to determine the expression of AT1-R and MCP-1. For the in vitro experiment, hPMVECs were divided into control, AngII group, AngII+Bindarit group and Bindarit group, respectively. Flow cytometry was performed to analyze the apoptosis in each group. Reverse transcription-polymerase chain reaction was performed to determine the mRNA expression of MCP-1. Western blot analysis was performed to evaluate the expression of MCP-1 and apoptosis related protein. Apoptosis of hPMVECs was observed in the lung tissues in the cadavers with AAD complicated with ALI. Besides, the expression of AT1-R and MCP-1 was remarkably elevated. Compared with normal individuals and the non-lung injury AAD patients, the expression of serum AngII was remarkably elevated in AAD patients complicated with ALI. In vitro experiments showed AngII contributed to the apoptosis and elevation of MCP1 in hPMVECs. Besides, it involved in the down-regulation of Bcl-2 protein, and up-regulation of Bax and Caspase-3. Such phenomenon was completely reversed after administration of MCP-1 inhibitor (Bindarit). The production of MCP-1 and cellular

  6. Aortic valve replacement

    DEFF Research Database (Denmark)

    Kapetanakis, Emmanouil I; Athanasiou, Thanos; Mestres, Carlos A

    2008-01-01

    BACKGROUND AND AIMS OF THE STUDY: Prompted by anecdotal evidence and observations by surgeons, an investigation was undertaken into the potential differences in implanted aortic valve prosthesis sizes, during aortic valve replacement (AVR) procedures, between northern and southern European...... countries. METHODS: A multi-institutional, non-randomized, retrospective analysis was conducted among 2,932 patients who underwent AVR surgery at seven tertiary cardiac surgery centers throughout Europe. Demographic and perioperative variables including valve size and type, body surface area (BSA) and early...

  7. Including aortic valve morphology in computational fluid dynamics simulations: initial findings and application to aortic coarctation.

    Science.gov (United States)

    Wendell, David C; Samyn, Margaret M; Cava, Joseph R; Ellwein, Laura M; Krolikowski, Mary M; Gandy, Kimberly L; Pelech, Andrew N; Shadden, Shawn C; LaDisa, John F

    2013-06-01

    Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  8. Aortic arch mechanics measured with two-dimensional speckle tracking echocardiography.

    Science.gov (United States)

    Teixeira, Rogério; Monteiro, Ricardo; Baptista, Rui; Pereira, Telmo; Ribeiro, Miguel A; Gonçalves, Alexandra; Cardim, Nuno; Gonçalves, Lino

    2017-07-01

    To study the feasibility of vascular mechanics at the aortic arch with two-dimensional speckle tracking echocardiography, as well as to define normal values and to compare results between hypertensive patients and healthy patients. We included 107 patients (61 healthy patients and 46 hypertensive patients) who underwent a complete echocardiographic exam, including a short-axis view of the aortic arch. The speckle tracking methodology was used to calculate aortic arch mechanics offline (EchoPAC; GE Healthcare). The analysis was performed for circumferential aortic strain and for the early circumferential aortic strain rate, and we used an average result of the six equidistant segments of the arterial wall. We also assessed the aortic pulse wave velocity with the Complior method. The 61 healthy patients had a mean age of 33 ± 9 years, and 59% were women. Of the total 366 aortic arch wall segments, 344 (94%) had adequate waveforms for the speckle tracking analysis. The hypertensive patients had a mean age of 45 ± 12 years, and 54% were women. Of the total 276 aortic wall segments, 261 (95%) had adequate waveforms for analysis. Aortic arch strain and strain rate were lower in the hypertensive patients group than in the healthy patients group (6.3 ± 2.0 vs. 11.2 ± 3.2% and 1.0 ± 0.3 vs. 1.5 ± 0.4 s, respectively, both P Speckle tracking analysis of aortic arch images is feasible and might serve as a new approach to evaluate arterial function.

  9. Blood flow characteristics in the ascending aorta after TAVI compared to surgical aortic valve replacement.

    Science.gov (United States)

    Trauzeddel, Ralf Felix; Löbe, Ulrike; Barker, Alex J; Gelsinger, Carmen; Butter, Christian; Markl, Michael; Schulz-Menger, Jeanette; von Knobelsdorff-Brenkenhoff, Florian

    2016-03-01

    Ascending aortic blood flow characteristics are altered after aortic valve surgery, but the effect of transcatheter aortic valve implantation (TAVI) is unknown. Abnormal flow may be associated with aortic and cardiac remodeling. We analyzed blood flow characteristics in the ascending aorta after TAVI in comparison to conventional stented aortic bioprostheses (AVR) and healthy subjects using time-resolved three-dimensional flow-sensitive cardiovascular magnetic resonance imaging (4D-flow MRI). Seventeen patients with TAVI (Edwards Sapien XT), 12 with AVR and 9 healthy controls underwent 4D-flow MRI of the ascending aorta. Target parameters were: severity of vortical and helical flow pattern (semiquantitative grading from 0 = none to 3 = severe) and the local distribution of systolic wall shear stress (WSSsystole). AVR revealed significantly more extensive vortical and helical flow pattern than TAVI (p = 0.042 and p = 0.002) and controls (p flow than controls (p blood flow eccentricity (64.7 and 66.7%, respectively), whereas controls showed central blood flow (88.9%). TAVI and AVR exhibited an asymmetric distribution of WSSsystole in the mid-ascending aorta with local maxima at the right anterior aortic wall and local minima at the left posterior wall. In contrast, controls showed a symmetric distribution of WSSsystole along the aortic circumference. Blood flow was significantly altered in the ascending aorta after TAVI and AVR. Changes were similar regarding WSSsystole distribution, while TAVI resulted in less helical and vortical blood flow.

  10. EXPRESSION OF MATRIX METALLOPROTEINASE-9 IN HUMANABDOMINAL AORTIC ANEURYSMAL TISSUES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Abdominal aortic aneuryzms(AAAs)are char-acterized by the degradation of structural proteins,including both collagen and elastin and remodelingof the extracellular matrix(ECM).The matrixmetalloproteinases(MMPs)are responsible for col-lagen and elastin degradation withinthe aortic wall.Up to date,14MMPs have beenidentified.Amongthem,in particular,MMP-9(92-kDtypeⅣcolla-genase)shows strong elastinolytic activity[1].Recentstudies showedthat elevated plasmalevel of MMP-9wasassociated with AAAs,i mplicating its p...

  11. Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes

    Science.gov (United States)

    Jia, Yijun; Weng, Ziyi; Wang, Chuanying; Zhu, Mingjie; Lu, Yunshu; Ding, Longlong; Wang, Yongkun; Cheng, Xianhua; Lin, Qing; Wu, Kejin

    2017-01-01

    Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O2-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80.

  12. Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates.

    Directory of Open Access Journals (Sweden)

    Pei-Wen Tsai

    Full Text Available Candida albicans is the major fungal pathogen of humans. Fungal adhesion to host cells is the first step of mucosal infiltration. Antimicrobial peptides play important roles in the initial mucosal defense against C. albicans infection. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides and is commonly expressed in various tissues and cells, including epithelial cells of both the oral cavity and urogenital tract. We found that, at sufficiently low concentrations that do not kill the fungus, LL-37 was still able to reduce C. albicans infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. Moreover, LL-37-treated C. albicans floating cells that did not adhere to the underlying substratum aggregated as a consequence of LL-37 bound to the cell surfaces. According to the results of a competition assay, the inhibitory effects of LL-37 on cell adhesion and aggregation were mediated by its preferential binding to mannan, the main component of the C. albicans cell wall, and partially by its ability to bind chitin or glucan, which underlie the mannan layer. Therefore, targeting of cell-wall carbohydrates by LL-37 provides a new strategy to prevent C. albicans infection, and LL-37 is a useful, new tool to screen for other C. albicans components involved in adhesion.

  13. Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein

    Science.gov (United States)

    Jiang, Wen-Jian; Ren, Wei-Hong; Liu, Xu-Jie; Liu, Yan; Wu, Fu-Jian; Sun, Li-Zhong; Lan, Feng; Du, Jie; Zhang, Hong-Jia

    2016-01-01

    In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro, and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome. PMID:27608489

  14. Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein.

    Science.gov (United States)

    Jiang, Wen-Jian; Ren, Wei-Hong; Liu, Xu-Jie; Liu, Yan; Wu, Fu-Jian; Sun, Li-Zhong; Lan, Feng; Du, Jie; Zhang, Hong-Jia

    2016-09-05

    In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro, and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome.

  15. Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

    DEFF Research Database (Denmark)

    Kloster, Brian Ozeraitis; Lund, Lars; Lindholt, Jes S.

    2015-01-01

    BACKGROUND: A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. METHODS: 10...... ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. RESULTS: In group A, all pigs developed continuous expanding AAA's with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11...... in group A. The most frequent complication was a neurological deficit in the lower limbs. CONCLUSION: In pigs it's possible to induce continuous expanding AAA's based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved...

  16. Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

    Science.gov (United States)

    Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

    2016-08-16

    Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results.

  17. Enhancing 4D PC-MRI in an aortic phantom considering numerical simulations

    Science.gov (United States)

    Kratzke, Jonas; Schoch, Nicolai; Weis, Christian; Müller-Eschner, Matthias; Speidel, Stefanie; Farag, Mina; Beller, Carsten J.; Heuveline, Vincent

    2015-03-01

    To date, cardiovascular surgery enables the treatment of a wide range of aortic pathologies. One of the current challenges in this field is given by the detection of high-risk patients for adverse aortic events, who should be treated electively. Reliable diagnostic parameters, which indicate the urge of treatment, have to be determined. Functional imaging by means of 4D phase contrast-magnetic resonance imaging (PC-MRI) enables the time-resolved measurement of blood flow velocity in 3D. Applied to aortic phantoms, three dimensional blood flow properties and their relation to adverse dynamics can be investigated in vitro. Emerging "in silico" methods of numerical simulation can supplement these measurements in computing additional information on crucial parameters. We propose a framework that complements 4D PC-MRI imaging by means of numerical simulation based on the Finite Element Method (FEM). The framework is developed on the basis of a prototypic aortic phantom and validated by 4D PC-MRI measurements of the phantom. Based on physical principles of biomechanics, the derived simulation depicts aortic blood flow properties and characteristics. The framework might help identifying factors that induce aortic pathologies such as aortic dilatation or aortic dissection. Alarming thresholds of parameters such as wall shear stress distribution can be evaluated. The combined techniques of 4D PC-MRI and numerical simulation can be used as complementary tools for risk-stratification of aortic pathology.

  18. Non coding RNAs in aortic aneurysmal disease

    Directory of Open Access Journals (Sweden)

    Aparna eDuggirala

    2015-04-01

    Full Text Available An aneurysm is a local dilatation of a vessel wall which is >50% its original diameter. Withinthe spectrum of cardiovascular diseases, aortic aneurysms are among the most challenging to treat. Most patients present acutely after aneurysm rupture or dissection from a previous asymptomatic condition and are managed by open surgical or endovascular repair. In addition, patients may harbour concurrent disease contraindicating surgical intervention. Collectively, these factors have driven the search for alternative methods of identifying, monitoring and treating aortic aneurisms using less invasive approaches. Non-coding RNA (ncRNAs are emerging as new fundamental regulators of gene expression. The small microRNAs have opened the field of ncRNAs capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers for aortic aneurysm. More recently, long ncRNAs (lncRNAs have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease.

  19. Unoperated aortic aneurysm

    DEFF Research Database (Denmark)

    Perko, M J; Nørgaard, M; Herzog, T M;

    1995-01-01

    From 1984 to 1993, 1,053 patients were admitted with aortic aneurysm (AA) and 170 (15%) were not operated on. The most frequent reason for nonoperative management was presumed technical inoperability. Survivals for patients with thoracic, thoracoabdominal, and abdominal AA were comparable...... hypertension were predictive of mortality, whereas...

  20. Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation

    DEFF Research Database (Denmark)

    Sun, J; Zhang, J; Lindholt, Jes S.

    2009-01-01

    Mast cell chymase may participate in the pathogenesis of human abdominal aortic aneurysm (AAA), yet a direct contribution of this serine protease to AAA formation remains unknown.......Mast cell chymase may participate in the pathogenesis of human abdominal aortic aneurysm (AAA), yet a direct contribution of this serine protease to AAA formation remains unknown....

  1. [The thickness/radius ratio of the left ventricle in aortic stenosis. Prognostic and therapeutic implications].

    Science.gov (United States)

    Guadalajara, J F; Martínez, C; Huerta, D

    1990-01-01

    Using two-D echocardiography and cardiac catheterization we studied the performance of left ventricle in severe aortic stenosis with normal ventricular function (10 patients), and with heart failure (11 patients). With appropriate hypertrophy increased ventricular function, is found resulting in systolic wall stress normalization. When hypertrophic mechanism is unable to normalize the systolic wall stress; afterload increases with ensuing heart failure (inadequate hypertrophy). Surgical treatment in those cases reduces the afterload and increases de ventricular function. Normalization of systolic wall stress in patients with severe aortic stenosis and heart failure means irreversible myocardial damage.

  2. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H. (Univ. of Southern California School of Medicine, Los Angeles (USA))

    1990-06-01

    Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with (111In)nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

  3. Thoracic aortic aneurysm: reading the enemy's playbook.

    Science.gov (United States)

    Elefteriades, John A

    2008-05-01

    The vast database of the Yale Center for Thoracic Aortic Disease--which includes information on 3000 patients with thoracic aortic aneurysm or dissection, with 9000 catalogued images and 9000 patient-years of follow-up--has, over the last decade, permitted multiple glimpses into the "playbook" of this virulent disease. Understanding the precise behavioral features of thoracic aortic aneurysm and dissection permits us more effectively to combat this disease. In this monograph, we will first review certain fundamentals--in terms of anatomy, nomenclature, imaging, diagnosis, medical, surgical, and stent treatment. After reviewing these fundamentals, we will proceed with a detailed exploration of lessons learned by peering into the operational playbook of thoracic aortic aneurysm and dissection. Among the glimpses afforded in the behavioral playbook of this disease are the following: 1 Thoracic aortic aneurysm, while lethal, is indolent. Mortality usually does not occur until after years of growth. 2 The aneurysmal ascending thoracic aorta grows slowly: about 0.1 cm per year (the descending aorta grows somewhat faster). 3 Over a patient's lifetime, "hinge points" at which the likelihood of rupture or dissection skyrockets are seen at 5.5 cm for the ascending and 6.5 cm for the descending aorta. Intervening at 5 cm diameter for the ascending and 6 cm for the descending prevents most adverse events. 4 Symptomatic aneurysms require resection regardless of size. 5 The yearly rate of rupture, dissection, or death is 14.1% for a patient with a thoracic aorta of 6 cm diameter. 6 The mechanical properties of the aorta deteriorate markedly at 6 cm diameter (distensibility falls, and wall stress rises)--a finding that "dovetails" perfectly with observations of the clinical behavior of the thoracic aorta. 7 Thoracic aortic aneurysm and dissection are largely inherited diseases, with a predominantly autosomal-dominant pattern. The specific genetics are being elucidated at the

  4. HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Pasquinelli Gianandrea

    2011-05-01

    Full Text Available Abstract Background HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs. Results MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPARγ activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. Conclusions The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients.

  5. Extended aortic valvuloplasty: a new approach for the management of congenital valvar aortic stenosis.

    Science.gov (United States)

    Ilbawi, M N; DeLeon, S Y; Wilson, W R; Roberson, D A; Husayni, T S; Quinones, J A; Arcilla, R A

    1991-09-01

    A new technique for the treatment of congenital valvar aortic stenosis is described. It consists of augmenting the aortic cusp by extending the commissurotomy incision into the aortic wall around the leaflet insertion, mobilizing the valve cusp attachment at the commissures, and freeing the aortic insertion of the rudimentary commissure. The results of standard valvotomy performed on 48 patients (group 1) were compared with those of the new extended valvuloplasty carried out on 16 patients (group 2). The two groups were comparable in age at operation (2.7 +/- 2.1 years for group 1 versus 2.1 +/- 1.7 years for group 2; p = not significant) and in preoperative pressure gradient (58 +/- 25 mm Hg for group 1 versus 61 +/- 36 mm Hg for group 2; p = not significant). There was no operative mortality in either group. Follow-up is available on all patients, with a mean of 4.3 +/- 2.6 years for group 1 versus 1.7 +/- 0.5 years for group 2 (p = 0.05). There was one late death in group 1. Postoperative gradient was 47 +/- 13 mm Hg in group 1 versus 19 +/- 13 mm Hg in group 2 (p = 0.05). Moderate or severe regurgitation was present in 18 patients (38%) in group 1 and 2 patients (13%) in group 2 (p = not significant). Reoperation was needed in 8 patients (17%) in group 1 versus 2 patients (13%) in group 2 (p = not significant). The described valvuloplasty procedure addresses the unique pathological features of valvar aortic stenosis and provides better relief of the obstruction than the presently available techniques. Longer follow-up is needed to determine the late results of this approach.

  6. [Stanford type a acute aortic dissection with pectus excavatum].

    Science.gov (United States)

    Kuwata, Toshiyuki; Fukuda, Hirotsugu; Yoshitatsu, Masao; Yamada, Yasuyuki; Shibasaki, Ikuko; Inoue, Yuho; Hori, Takayuki; Ogawa, Hironaga; Tsuchiya, Go; Shimizu, Riha; Takei, Yusuke

    2012-11-01

    Pectus excavatum is generally an isolated abnormality of the chest wall. However, some patients have a concomitant pectus deformity and cardiac & aortic disease. Decisions must be made regarding the operative approach and whether the pectus excavatum should be corrected during the same session. We report 2 patients with acute Stanford type A aortic dissection and pectus excavatum who underwent emergency operation. In case 1, median sternotomy is an unsuitable approach for open heart surgery, since the heart and great vessels are displace into the left hemithorax. But combined sternotomy and left anterior thoracotomy provided excellent surgical exposure. In case 2, we proceeded with a leftsided costotomy of four ribs and place a normal chest retractor providing as excellent exposure as combined sternotomy and left anterior thoracotomy. A left-sided costotomy of four ribs can be performed safely, eliminating the risks of median sternotomy in acute stanford type A aortic dissection with pectus excavatum.

  7. Simulation of bifurcated stent grafts to treat abdominal aortic aneurysms (AAA)

    CERN Document Server

    Egger, Jan; Freisleben, Bernd

    2016-01-01

    In this paper a method is introduced, to visualize bifurcated stent grafts in CT-Data. The aim is to improve therapy planning for minimal invasive treatment of abdominal aortic aneurysms (AAA). Due to precise measurement of the abdominal aortic aneurysm and exact simulation of the bifurcated stent graft, physicians are supported in choosing a suitable stent prior to an intervention. The presented method can be used to measure the dimensions of the abdominal aortic aneurysm as well as simulate a bifurcated stent graft. Both of these procedures are based on a preceding segmentation and skeletonization of the aortic, right and left iliac. Using these centerlines (aortic, right and left iliac) a bifurcated initial stent is constructed. Through the implementation of an ACM method the initial stent is fit iteratively to the vessel walls - due to the influence of external forces (distance- as well as balloonforce). Following the fitting process, the crucial values for choosing a bifurcated stent graft are measured, ...

  8. Tissue Responses to Stent Grafts with Endo-Exo-Skeleton for Saccular Abdominal Aortic Aneurysms in a Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il Young; Chung, Jin Wook; Kim, Hyo Cheol [Dept. of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul (Korea, Republic of); Choi, Young Ho; So Young Ho [Dept. of Radiology, Seoul National University Boramae Hospital, Seoul (Korea, Republic of); Kim, Hyun Beom [Dept. of Radiology, National Cancer Center, Goyang (Korea, Republic of); Min, Seung Kee [Dept. of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Jae Hyung [Dept. of Radiology, Gachon University Gil Medical Center, Incheon (Korea, Republic of)

    2014-10-15

    We evaluated the effect of close contact between the stent and the graft on the induction of endothelial covering on the stent graft placed over an aneurysm. Saccular abdominal aortic aneurysms were made with Dacron patch in eight dogs. The stent graft consisted of an inner stent, a expanded polytetrafluoroethylene graft, and an outer stent. After sacrificing the animals, the aortas with an embedded stent graft were excised. The aortas were inspected grossly and evaluated microscopically. The animals were sacrificed at two (n = 3), six (n = 3), and eight months (n = 2) after endovascular repair. In two dogs, the aortic lumen was occluded at two months after the placement. On gross inspection of specimens from the other six dogs with a patent aortic lumen, stent grafts placed over the normal aortic wall were covered by glossy white neointima, whereas, stent grafts placed over the aneurysmal aortic wall were covered by brownish neointima. On microscopic inspection, stent grafts placed over the normal aortic wall were covered by thin neointima (0.27 ± 0.05 mm, mean ± standard deviation) with an endothelial layer, and stent grafts placed over the aneurysmal aortic wall were covered by thick neointima (0.62 ± 0.17 mm) without any endothelial lining. Transgraft cell migration at the normal aortic wall was more active than that at the aneurysmal aortic wall. Close contact between the stent and the graft, which was achieved with stent grafts with endo-exo-skeleton, could not enhance endothelial covering on the stent graft placed over the aneurysms.

  9. Influence of carboxylic acid functionalization on the cytotoxic effects induced by single wall carbon nanotubes on human endothelial cells (HUVEC).

    Science.gov (United States)

    Gutiérrez-Praena, Daniel; Pichardo, Silvia; Sánchez, Elena; Grilo, Antonio; Cameán, Ana Maria; Jos, Angeles

    2011-12-01

    A vast variety of nanomaterials have been developed in the recent years, being carbon nanotubes (CNTs) the ones that have attracted more attention, due to its unique properties which make them suitable for numerous applications. Consequently, it is predicted that tons of CNTs will be produced worldwide every year, being its exposure of toxicological concern. Nanomaterials, once into the body, can translocate from the uptake sites to the blood circulation or the lymphatic system, resulting in distribution throughout the body. Thus, the vascular endothelium can be in contact with them and can suffer from their toxic effects. In this regard, the aim of this work was to investigate the cytotoxicity of single-walled carbon nanotubes (SWCNTs) on human endothelial cells evaluating the influence of acid carboxylic functionalization and also the exposure time (24 and 48 h). Biomarkers assessed were neutral red uptake, protein content, a tetrazolium salt metabolization and cell viability by means of the Trypan blue exclusion test. Cells were exposed to concentrations between 0 and 800 μg/mL SWCNTs for 24 and 48 h. Results have shown that both SWCNTs and carboxylic acid functionalized single-walled carbon nanotubes (COOH-SWCNTs) induce toxic effects in HUVEC cells in a concentration- and time-dependent way. Moreover, the carboxylic acid functionalization results in a higher toxicity compared to the SWCNTs.

  10. Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.

    Science.gov (United States)

    Peters, Sheila Annie; Jones, Christopher R; Ungell, Anna-Lena; Hatley, Oliver J D

    2016-06-01

    Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. The primary objective of this review is to summarize the current knowledge in the quantitative prediction of gut-wall metabolism. As well as discussing the successes of current models for intestinal metabolism, the challenges in the establishment of good preclinical models are highlighted, including species differences in the isoforms; regional abundances and activities of drug metabolizing enzymes; the interplay of enzyme-transporter proteins; and lack of knowledge on enzyme abundances and availability of empirical scaling factors. Due to its broad specificity and high abundance in the intestine, CYP3A is the enzyme that is frequently implicated in human gut metabolism and is therefore the major focus of this review. A strategy to assess the impact of gut wall metabolism on oral bioavailability during drug discovery and early development phases is presented. Current gaps in the mechanistic understanding and the prediction of gut metabolism are highlighted, with suggestions on how they can be overcome in the future.

  11. Flow-sensitive in-vivo 4D MR imaging at 3T for the analysis of aortic hemodynamics and derived vessel wall parameters; Die Analyse aortaler Haemodynamik und Gefaesswandparameter mittels fluss-sensitiver in-vivo 4D-MRT bei 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Frydrychowicz, A.; Markl, M.; Stalder, A.F.; Bock, J.; Bley, T.A.; Berger, A.; Russe, M.F.; Hennig, J.; Langer, M. [Freiburg Univ. (Germany). Abt. Roentgendiagnostik; Harloff, A. [Freiburg Univ. (Germany). Abt. Klinische Neurologie und Neurophysiologie; Schlensak, C. [Freiburg Univ. (Germany). Abt. Herz- und Gefaesschirurgie

    2007-05-15

    Modern phase contrast MR imaging at 3 Tesla allows the depiction of 3D morphology as well as the acquisition of time-resolved blood flow velocities in 3 directions. In combination with state-of-the-art visualization and data processing software, the qualitative and quantitative analysis of hemodynamic changes associated with vascular pathologies is possible. The 4D nature of the acquired data permits free orientation within the vascular system of interest and offers the opportunity to quantify blood flow and derived vessel wall parameters at any desired location within the data volume without being dependent on predefined 2D slices. The technique has the potential of overcoming the limitations of current diagnostic strategies and of implementing new diagnostic parameters. In light of the recent discussions regarding the influence of the wall shear stress and the oscillatory shear index on the genesis of arteriosclerosis and dilatative vascular processes, flow-sensitive 4D MRI may provide the missing diagnostic link. Instead of relying on experience-based parameters such as aneurysm size, new hemodynamic considerations can deepen our understanding of vascular pathologies. This overview reviews the underlying methodology at 3T, the literature on time-resolved 3D MR velocity mapping, and presents case examples. By presenting the pre- and postoperative assessment of hemodynamics in a thoracic aortic aneurysm and the detailed analysis of blood flow in a patient with coarctation we underline the potential of time-resolved 3D phase contrast MR at 3T for hemodynamic assessment of vascular pathologies, especially in the thoracic aorta. (orig.)

  12. Mast Cells in Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Shi, Guo-Ping; Lindholt, Jes Sanddal

    2013-01-01

    Mast cells (MCs) are proinflammatory cells that play important roles in allergic responses, tumor growth, obesity, diabetes, atherosclerosis, and abdominal aortic aneurysm (AAA). Although the presence and function of MCs in atherosclerotic lesions have been thoroughly studied in human specimens...... neighboring cells, degrade extracellular matrix proteins, process latent bioactive molecules, promote angiogenesis, recruit additional inflammatory cells, and stimulate vascular cell apoptosis. These activities associate closely with medial elastica breakdown, medial smooth-muscle cell loss and thinning...

  13. Detection and Classification of Finer-Grained Human Activities Based on Stepped-Frequency Continuous-Wave Through-Wall Radar.

    Science.gov (United States)

    Qi, Fugui; Liang, Fulai; Lv, Hao; Li, Chuantao; Chen, Fuming; Wang, Jianqi

    2016-06-15

    The through-wall detection and classification of human activities are critical for anti-terrorism, security, and disaster rescue operations. An effective through-wall detection and classification technology is proposed for finer-grained human activities such as piaffe, picking up an object, waving, jumping, standing with random micro-shakes, and breathing while sitting. A stepped-frequency continuous wave (SFCW) bio-radar sensor is first used to conduct through-wall detection of finer-grained human activities; Then, a comprehensive range accumulation time-frequency transform (CRATFR) based on inverse weight coefficients is proposed, which aims to strengthen the micro-Doppler features of finer activity signals. Finally, in combination with the effective eigenvalues extracted from the CRATFR spectrum, an optimal self-adaption support vector machine (OS-SVM) based on prior human position information is introduced to classify different finer-grained activities. At a fixed position (3 m) behind a wall, the classification accuracies of six activities performed by eight individuals were 98.78% and 93.23%, respectively, for the two scenarios defined in this paper. In the position-changing experiment, an average classification accuracy of 86.67% was obtained for five finer-grained activities (excluding breathing) of eight individuals within 6 m behind the wall for the most practical scenario, a significant improvement over the 79% accuracy of the current method.

  14. Detection and Classification of Finer-Grained Human Activities Based on Stepped-Frequency Continuous-Wave Through-Wall Radar

    Directory of Open Access Journals (Sweden)

    Fugui Qi

    2016-06-01

    Full Text Available The through-wall detection and classification of human activities are critical for anti-terrorism, security, and disaster rescue operations. An effective through-wall detection and classification technology is proposed for finer-grained human activities such as piaffe, picking up an object, waving, jumping, standing with random micro-shakes, and breathing while sitting. A stepped-frequency continuous wave (SFCW bio-radar sensor is first used to conduct through-wall detection of finer-grained human activities; Then, a comprehensive range accumulation time-frequency transform (CRATFR based on inverse weight coefficients is proposed, which aims to strengthen the micro-Doppler features of finer activity signals. Finally, in combination with the effective eigenvalues extracted from the CRATFR spectrum, an optimal self-adaption support vector machine (OS-SVM based on prior human position information is introduced to classify different finer-grained activities. At a fixed position (3 m behind a wall, the classification accuracies of six activities performed by eight individuals were 98.78% and 93.23%, respectively, for the two scenarios defined in this paper. In the position-changing experiment, an average classification accuracy of 86.67% was obtained for five finer-grained activities (excluding breathing of eight individuals within 6 m behind the wall for the most practical scenario, a significant improvement over the 79% accuracy of the current method.

  15. Transforming growth factor-β and abdominal aortic aneurysms.

    Science.gov (United States)

    Wang, Yutang; Krishna, Smriti; Walker, Philip J; Norman, Paul; Golledge, Jonathan

    2013-01-01

    Abdominal aortic aneurysms (AAAs) are common problems in aged people which can be associated with severe complications including aortic rupture and death. Transforming growth factor-β (TGFβ) has been implicated as causative in the development of thoracic aortic aneurysms (TAAs). In contrast, current evidence suggests TGFβ inhibits AAA development. Polymorphisms in the TGFβ signaling components are associated with AAA in some human population studies. In experimental animals TGFβ protects against AAA formation, progression and rupture. In animal models of AAA TGFβ decreases aortic inflammatory cell infiltration, extracellular matrix degradation, and vascular smooth muscle cell apoptosis, all factors implicated in AAA pathogenesis. The TGFβ signaling pathway may provide a therapeutic target for AAA although better clarity is needed regarding the distinct roles of TGFβ in TAA and AAA.

  16. Mesothelial/monocytic incidental cardiac excrescences (cardiac MICE) associated with acute aortic dissection: a study of two cases

    Science.gov (United States)

    Strecker, Thomas; Bertz, Simone; Wachter, David Lukas; Weyand, Michael; Agaimy, Abbas

    2015-01-01

    Acute aortic dissection is a life-threatening condition mainly caused by hypertension, atherosclerotic disease and other degenerative diseases of the connective tissue of the aortic wall. Mesothelial/monocytic incidental cardiac excrescences (cardiac MICE) is a rare benign reactive tumor-like lesion composed of admixture of histiocytes, mesothelial cells, and inflammatory cells set within a fibrinous meshwork without a vascular network or supporting stroma. Cardiac MICE occurring in association with aortic dissection is exceptionally rare (only one such case reported to date). We herein report on the surgical repair of two Stanford type A aortic dissections caused by idiopathic giant cell aortitis in a 66-year-old-woman and by atherosclerotic disease in a 58-year-old-man, respectively. In both cases, the dissections could be visualized via computed tomography. Histopathology showed cardiac incidental MICE within the external aortic wall near the pericardial surface which was confirmed by immunohistochemistry. PMID:26097568

  17. Single-walled carbon nanotubes induce cytotoxicity and DNA damage via reactive oxygen species in human hepatocarcinoma cells.

    Science.gov (United States)

    Alarifi, Saud; Ali, Daoud; Verma, Ankit; Almajhdi, Fahad N; Al-Qahtani, Ahmed A

    2014-09-01

    Carbon nanotubes (CNTs) are gradually used in various areas including drug delivery, nanomedicine, biosensors, and electronics. The current study aimed to explore the DNA damage and cytotoxicity due to single-walled carbon nanotubes (SWCNTs) on human hepatocarcinoma cells (HepG2). Cellular proliferative assay showed the SWCNTs to exhibit a significant cell death in a dose- and time-dependent manner. However, SWCNTs induced significant intracellular reactive oxygen species (ROS) production and elevated lipid peroxidation, catalase, and superoxide dismutase in the HepG2 cells. SWCNTs also induced significant decrease in GSH and increase caspase-3 activity in HepG2 cells. DNA fragmentation analysis using the alkaline single-cell gel electrophoresis showed that the SWCNTs cause genotoxicity in a dose- and time-dependent manner. Therefore, the study points towards the capability of the SWCNTs to induce oxidative stress resulting cytotoxicity and genomic instability. This study warrants more careful assessment of SWCNTs before their industrial applications.

  18. Conducting polymer functionalized single-walled carbon nanotube based chemiresistive biosensor for the detection of human cardiac myoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Puri, Nidhi [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012 (India); Department of Physics, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025 (India); Niazi, Asad [Department of Physics, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025 (India); Biradar, Ashok M.; Rajesh, E-mail: rajesh-csir@yahoo.com, E-mail: adani@engr.ucr.edu [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012 (India); Mulchandani, Ashok, E-mail: rajesh-csir@yahoo.com, E-mail: adani@engr.ucr.edu [Department of Chemical and Environmental Engineering, University of California, Riverside, California 92521 (United States)

    2014-10-13

    We report the fabrication of a single-walled carbon nanotube (SWNT) based ultrasensitive label-free chemiresistive biosensor for the detection of human cardiac biomarker, myoglobin (Ag-cMb). Poly(pyrrole-co-pyrrolepropylic acid) with pendant carboxyl groups was electrochemically deposited on electrophoretically aligned SWNT channel, as a conducting linker, for biomolecular immobilization of highly specific cardiac myoglobin antibody. The device was characterized by scanning electron microscopy, source-drain current-voltage (I-V), and charge-transfer characteristic studies. The device exhibited a linear response with a change in conductance in SWNT channel towards the target, Ag-cMb, over the concentration range of 1.0 to 1000 ng ml{sup −1} with a sensitivity of ∼118% per decade with high specificity.

  19. Tobacco smoking and aortic aneurysm

    DEFF Research Database (Denmark)

    Sode, Birgitte F; Nordestgaard, Børge G; Grønbæk, Morten

    2012-01-01

    BACKGROUND: We determined the predictive power of tobacco smoking on aortic aneurysm as opposed to other risk factors in the general population. METHODS: We recorded tobacco smoking and other risk factors at baseline, and assessed hospitalization and death from aortic aneurysm in 15,072 individuals...... General Population Study, respectively. According to the magnitude of the hazard ratios, tobacco consumption was the most important risk factor for hospitalization and death from aortic aneurysm, followed by male sex and hypertension in both cohorts. The population attributable risk of aortic aneurysm...... outcomes due to tobacco consumption was 64% and 47% in the Copenhagen City Heart Study and Copenhagen General Population Study, respectively, and ranked highest among population attributable risks of aortic aneurysm in both cohorts. The absolute 10-year risk for hospitalization or death from aortic...

  20. Plaque components affect wall stress in stented human carotid artery: A numerical study

    Science.gov (United States)

    Fan, Zhen-Min; Liu, Xiao; Du, Cheng-Fei; Sun, An-Qiang; Zhang, Nan; Fan, Zhan-Ming; Fan, Yu-Bo; Deng, Xiao-Yan

    2016-09-01

    Carotid artery stenting presents challenges of in-stent restenosis and late thrombosis, which are caused primarily by alterations in the mechanical environment of the artery after stent implantation. The present study constructed patient-specific carotid arterial bifurcation models with lipid pools and calcified components based on magnetic resonance imaging. We numerically analyzed the effects of multicomponent plaques on the distributions of von Mises stresses (VMSs) in the patient-specific models after stenting. The results showed that when a stent was deployed, the large soft lipid pool in atherosclerotic plaques cushioned the host artery and reduced the stress within the arterial wall; however, this resulted in a sharp increase of VMS in the fibrous cap. When compared with the lipid pool, the presence of the calcified components led to slightly increased stresses on the luminal surface. However, when a calcification was located close to the luminal surface of the host artery and the stenosis, the local VMS was elevated. Overall, compared with calcified components, large lipid pools severely damaged the host artery after stenting. Furthermore, damage due to the calcified component may depend on location.

  1. Plaque components affect wall stress in stented human carotid artery:A numerical study

    Institute of Scientific and Technical Information of China (English)

    Zhen-Min Fan; Xiao Liu; Cheng-Fei Du; An-Qiang Sun; Nan Zhang; Zhan-Ming Fan; Yu-Bo Fan; Xiao-Yan Deng

    2016-01-01

    Carotid artery stenting presents challenges of in-stent restenosis and late thrombosis, which are caused primarily by alterations in the mechanical environment of the artery after stent implantation. The present study con-structed patient-specific carotid arterial bifurcation models with lipid pools and calcified components based on magnetic resonance imaging. We numerically analyzed the effects of multicomponent plaques on the distributions of von Mises stresses (VMSs) in the patient-specific models after stenting. The results showed that when a stent was deployed, the large soft lipid pool in atherosclerotic plaques cushioned the host artery and reduced the stress within the arterial wall;how-ever, this resulted in a sharp increase of VMS in the fibrous cap. When compared with the lipid pool, the presence of the calcified components led to slightly increased stresses on the luminal surface. However, when a calcification was located close to the luminal surface of the host artery and the stenosis, the local VMS was elevated. Overall, compared with calcified components, large lipid pools severely dam-aged the host artery after stenting. Furthermore, damage due to the calcified component may depend on location.

  2. Invasive aspergillosis in the aortic arch with infectious Aspergillus lesions in pulmonary bullae

    Directory of Open Access Journals (Sweden)

    Isao Watanabe

    2015-03-01

    Full Text Available A patient with pulmonary bullae died of massive hemoptysis. At autopsy a hole was observed in the aortic wall. A microscopic examination indicated small Aspergillus lesions in pulmonary bullae and extensive necrotic lesions with Aspergillus hyphae in the media of the thoracic aorta. These findings led to a diagnosis of invasive aspergillosis in the aortic arch. This is a rare case in which Aspergillus invaded the aorta in a patient without hematologic neoplasms or neutropenia.

  3. Aortic Dissection of Unknown Origin in a Young Patient: A Case Report

    OpenAIRE

    Majid Hajimaghsoudi; Faeze Zeinali; Mehdi Bagherabadi; Morteza Saeedi

    2016-01-01

    Aortic dissection occurs when a tear develops in the wall of the aorta, which is rare in the young population. This fatal disorder is hard to diagnose, especially in young patients. We present the case of aortic dissection in a 15-year-old boy referred to the Emergency Department of Yazd University of Medical Sciences in November 2015. The patient presented to our department with sudden acute chest pain. Emergent computed tomography (CT) scanning of the brain, chest, and abdomen reflected bil...

  4. MAT2A mutations predispose individuals to thoracic aortic aneurysms.

    Science.gov (United States)

    Guo, Dong-chuan; Gong, Limin; Regalado, Ellen S; Santos-Cortez, Regie L; Zhao, Ren; Cai, Bo; Veeraraghavan, Sudha; Prakash, Siddharth K; Johnson, Ralph J; Muilenburg, Ann; Willing, Marcia; Jondeau, Guillaume; Boileau, Catherine; Pannu, Hariyadarshi; Moran, Rocio; Debacker, Julie; Bamshad, Michael J; Shendure, Jay; Nickerson, Deborah A; Leal, Suzanne M; Raman, C S; Swindell, Eric C; Milewicz, Dianna M

    2015-01-08

    Up to 20% of individuals who have thoracic aortic aneurysms or acute aortic dissections but who do not have syndromic features have a family history of thoracic aortic disease. Significant genetic heterogeneity is established for this familial condition. Whole-genome linkage analysis and exome sequencing of distant relatives from a large family with autosomal-dominant inheritance of thoracic aortic aneurysms variably associated with the bicuspid aortic valve was used for identification of additional genes predisposing individuals to this condition. A rare variant, c.1031A>C (p.Glu344Ala), was identified in MAT2A, which encodes methionine adenosyltransferase II alpha (MAT IIα). This variant segregated with disease in the family, and Sanger sequencing of DNA from affected probands from unrelated families with thoracic aortic disease identified another MAT2A rare variant, c.1067G>A (p.Arg356His). Evidence that these variants predispose individuals to thoracic aortic aneurysms and dissections includes the following: there is a paucity of rare variants in MAT2A in the population; amino acids Glu344 and Arg356 are conserved from humans to zebrafish; and substitutions of these amino acids in MAT Iα are found in individuals with hypermethioninemia. Structural analysis suggested that p.Glu344Ala and p.Arg356His disrupt MAT IIα enzyme function. Knockdown of mat2aa in zebrafish via morpholino oligomers disrupted cardiovascular development. Co-transfected wild-type human MAT2A mRNA rescued defects of zebrafish cardiovascular development at significantly higher levels than mRNA edited to express either the Glu344 or Arg356 mutants, providing further evidence that the p.Glu344Ala and p.Arg356His substitutions impair MAT IIα function. The data presented here support the conclusion that rare genetic variants in MAT2A predispose individuals to thoracic aortic disease.

  5. Svensson Class IV Ascending Aortic Dissection, Often Confused With Penetrating Ulcer

    Directory of Open Access Journals (Sweden)

    Mitsomoy Michel Francklyn

    2015-03-01

    Full Text Available We present the case of a 64 years old male patient who had recently suffered an infective aortic valve endocarditis (Streptococcus agalactiae complicated by embolic arthritis of the right hip. Initial echocardiography revealed moderate aortic insufficiency developed on a tricuspidaortic valve with a small vegetation (5 mm × 4 mm on the left coronary cusp. Furthermore, ananeurysmal dilatation of the ascending aorta (maximal diameter, 54 mm was noted. Other heartvalves and left ventricular function were considered normal. The patient completed a 4 weekscourse of antibiotherapy, and the right hip arthritis was treated by drainage and synovectomy.The patient was subsequently referred to surgery on an outpatient basis for the aneurysm of theascending aorta. Preoperative computed tomography showed localized aortic dissection of thetubular ascending aorta characterized by an intimal tear without medial hematoma but excentricbulging of the aortic wall. This lesion was initially considered a penetrating ulcer of the aortic wallThe operative specimen allowed to make differential diagnosis with a penetrating aortic ulcer byshowing that the lesion did not develop within an atherosclerotic plaque. However, downstreamextension of the dissection was probably limited by the presence of transmural calcifications on itsdistal side. The patient underwent successful complete aortic root replacement using a stentlessFreestyle bioprosthesis with Dacron graft extension as reported previously

  6. Stanford-A acute aortic dissection, inflammation, and metalloproteinases: a review.

    Science.gov (United States)

    Cifani, Noemi; Proietta, Maria; Tritapepe, Luigi; Di Gioia, Cira; Ferri, Livia; Taurino, Maurizio; Del Porto, Flavia

    2015-01-01

    Acute aortic dissection (AAD) is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year. Depending on the site of rupture, AAD is classified as Stanford-A when the ascending aortic thoracic tract and/or the arch are involved, and Stanford-B when the descending thoracic aorta and/or aortic abdominal tract are targeted. It was recently shown that inflammatory pathways underlie aortic rupture in both type A and type B Stanford AAD. An immune infiltrate has been found within the middle and outer tunics of dissected aortic specimens. It has also been observed that the recall and activation of macrophages inside the middle tunic are key events in the early phases of AAD. Macrophages are able to release metalloproteinases (MMPs) and pro-inflammatory cytokines which, in turn, give rise to matrix degradation and neoangiogenesis. An imbalance between the production of MMPs and MMP tissue inhibitors is pivotal in the extracellular matrix degradation underlying aortic wall remodelling in dissections occurring both in inherited conditions and in atherosclerosis. Among MMPs, MMP-12 is considered a specific marker of aortic wall disease, whatever the genetic predisposition may be. The aim of this review is, therefore, to take a close look at the immune-inflammatory mechanisms underlying Stanford-A AAD.

  7. Particle Image Velocimetry studies of bicuspid aortic valve hemodynamics

    Science.gov (United States)

    Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P.

    2010-11-01

    Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses.

  8. Ruptured abdominal aortic aneurysm.

    Science.gov (United States)

    Sachs, T; Schermerhorn, M

    2010-06-01

    Ruptured abdominal aortic aneurysm (AAA) continues to be one of the most lethal vascular pathologies we encounter. Its management demands prompt and efficient evaluation and repair. Open repair has traditionally been the mainstay of treatment. However, the introduction of endovascular techniques has altered the treatment algorithm for ruptured AAA in most major medical centers. We present recent literature and techniques for ruptured AAA and its surgical management.

  9. Infrarenal Aortic Occlusion

    Science.gov (United States)

    Traverso, L. W.; Baker, J. D.; Dainko, E. A.; Machleder, H. I.

    1978-01-01

    Twenty-eight patients with total occlusion of the infrarenal aorta have been seen at the UCLA Hospitals in the past 11 years. Claudication was the presenting complaint in all but one patient, with one-third having ischemic rest pain. The average age of these patients was 54 years, and their histories revealed a surprising absence of myocardial infarction, stroke, or diabetes, although 40% had essential hypertension. Heavy tobacco use, however, was characteristic of the entire group. Arteriography proved valuable in identifying and characterizing the vascular abnormalities, but posed problems in technique and interpretation. Significant distal arterial disease was detected radiographically in only 21% of these patients. Operative correction of the aortic occlusion was performed on 26 patients, 18 by aortic bypass grafts and eight by aorto-iliac endarterectomy, with one early postoperative death. Although the thrombus extended to the renal artery origins in 77% of the cases, a well-designed technical approach did not require renal artery occlusion. Using serial creatinine determinations, one case of renal insufficiency was detected which was associated with prolonged postoperative hypotension. Although the extent of distal disease was more severe in those who underwent bypass, symptoms of claudication returned earlier and were more prominent in the endarterectomy group. This recurrence of systems was not favorably altered by sympathectomy performed concomitantly with the initial procedure. Even though this condition seems to pose difficult technical obstacles and has a poor prognosis, infrarenal aortic occlusion can be successfully treated by aortic bypass, with favorable long-term results, if particular attention is paid to elements of the preoperative evaluation and the intraoperative technical requirements peculiar to this relatively uncommon disease entity. ImagesFig. 1.Fig. 2.Fig. 3. PMID:646479

  10. Increased infiltration of Chlamydophila pneumoniae in the vessel wall of human veins after perfusion

    NARCIS (Netherlands)

    Kupreishvili, K.; Weeme, M.ter; Morré, S.A.; Brule, A.J.C. van den; Huybregts, M.A.J.M.; Quax, P.H.A.; Velden, J. ten; Hinsbergh, V.W.M. van; Stooker, W.; Eijsman, L.; Niessen, H.W.M.

    2008-01-01

    Background: Several studies have suggested an association between Chlamydophila pneumoniae (Cp) infection and atherosclerosis. A recent study detected Cp DNA in the saphenous vein of 12% of all patients before bypass grafting and in 38% of failed grafts. We used a system in which human veins were pe

  11. Mesenchymal stem cells for treatment of aortic aneurysms

    Institute of Scientific and Technical Information of China (English)

    Aika; Yamawaki-Ogata; Ryotaro; Hashizume; Xian-Ming; Fu; Akihiko; Usui; Yuji; Narita

    2014-01-01

    An aortic aneurysm(AA) is a silent but life-threatening disease that involves rupture. It occurs mainly in aging and severe atherosclerotic damage of the aortic wall. Even though surgical intervention is effective to prevent rupture, surgery for the thoracic and thoraco-abdom-inal aorta is an invasive procedure with high mortality and morbidity. Therefore, an alternative strategy for treatment of AA is required. Recently, the molecular pathology of AA has been clarified. AA is caused by an imbalance between the synthesis and degradation of extracellular matrices in the aortic wall. Chronic inflam-mation enhances the degradation of matrices directly and indirectly, making control of the chronic inflamma-tion crucial for aneurysmal development. Meanwhile, mesenchymal stem cells(MSCs) are known to be ob-tained from an adult population and to differentiate into various types of cells. In addition, MSCs have not only the potential anti-inflammatory and immunosuppres-sive properties but also can be recruited into damagedtissue. MSCs have been widely used as a source for celltherapy to treat various diseases involving graft-versus-host disease, stroke, myocardial infarction, and chronicinflammatory disease such as Crohn’s disease clinically.Therefore, administration of MSCs might be availableto treat AA using anti-inflammatory and immnosup-pressive properties. This review provides a summary ofseveral studies on "Cell Therapy for Aortic Aneurysm"including our recent data, and we also discuss the pos-sibility of this kind of treatment.

  12. 腹主动脉瘤动脉壁血管平滑肌细胞增殖及凋亡的研究%Vascular smooth muscle cell proliferation and apoptosis of the aortic wall during the development of abdominal aortic aneurysm

    Institute of Scientific and Technical Information of China (English)

    李大勇; 车艳; 杨镛; 张强; 吕延伟

    2004-01-01

    目的研究腹主动脉瘤(abdominal aortic aneurysm,AAA)在发病不同时期动脉壁平滑肌细胞(smooth muscle cells,SMC)增殖与凋亡的改变. 方法建立大鼠AAA模型,分别于术后3 d、1、2、3、4周切取腹主动脉,应用原位DNA片段末端标记(TUNEL)和免疫组织化学方法检测腹主动脉壁中SMC凋亡和相关基因bcl-2、bax蛋白以及增殖细胞核抗原(PCNA)、α-血管平滑肌肌动蛋白(α-actin)的表达. 结果 TUNEL及PCNA表达高峰时段分别为术后2~3周和1周;术后3 d至1周凋亡细胞少于PCNA阳性SMC,2~4周多于PCNA阳性SMC且SMC数量明显减少;bcl-2与bax蛋白表达分别于术后1、3周达到峰值(P<0.01). 结论动脉壁SMC增殖和凋亡的失衡与AAA发病密切相关;bcl-2与bax基因参与了对AAA动脉壁中SMC凋亡的调控.

  13. Effects of high-frequency chest wall oscillation on respiratory control in humans.

    Science.gov (United States)

    Khoo, M C; Gelmont, D; Howell, S; Johnson, R; Yang, F; Chang, H K

    1989-05-01

    We studied the spontaneous breathing patterns of 10 normal adult volunteers during high-frequency chest wall oscillation (HFCWO), accomplished by inflating and deflating a vest worn around each subject's thorax at 2.5 Hz. Tidal volumes generated by HFCWO averaged 100 ml. Mean vest pressure was maintained at approximately 35 cm H2O throughout each experiment, even when HFCWO was not applied. During HFCWO, subjects were instructed occasionally to exhale deeply to obtain end-tidal samples representative of PACO2. HFCWO increased the breath-to-breath variability of spontaneous respiration in all subjects, prolonging expiratory pauses and producing short apneas in some cases. PACO2 decreased significantly (p less than 0.05). The effects on minute ventilation, tidal volume, and inspiratory and expiratory durations remained variable across subjects, even when differences in PACO2 between control and HFCWO states were reduced through inhalation of a low CO2 mixture. None of the changes were statistically significant, although average expiratory duration increased by 29%. Ventilatory responses to CO2 with and without HFCWO were also measured. Normocapnic (PACO2 = 40 mm Hg) ventilatory drive increased significantly (p less than 0.05) in six subjects (Type 1 response) and decreased substantially in the others (Type 2 response); with hypercapnia, the changes in drive were attenuated in both groups. Consequently, CO2 sensitivity decreased in Type 1 subjects and increased in Type 2 subjects. A simple analysis based on this result shows that with HFCWO, Type 2 subjects breathing air will tend to have a lower spontaneous minute ventilation and become hypercapnic. Type 1 subjects will become hypocapnic, but minute ventilation may be higher or lower than control.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Molecular mapping of the cell wall polysaccharides of the human pathogen Streptococcus agalactiae

    Science.gov (United States)

    Beaussart, Audrey; Péchoux, Christine; Trieu-Cuot, Patrick; Hols, Pascal; Mistou, Michel-Yves; Dufrêne, Yves F.

    2014-11-01

    The surface of many bacterial pathogens is covered with polysaccharides that play important roles in mediating pathogen-host interactions. In Streptococcus agalactiae, the capsular polysaccharide (CPS) is recognized as a major virulence factor while the group B carbohydrate (GBC) is crucial for peptidoglycan biosynthesis and cell division. Despite the important roles of CPS and GBC, there is little information available on the molecular organization of these glycopolymers on the cell surface. Here, we use atomic force microscopy (AFM) and transmission electron microscopy (TEM) to analyze the nanoscale distribution of CPS and GBC in wild-type (WT) and mutant strains of S. agalactiae. TEM analyses reveal that in WT bacteria, peptidoglycan is covered with a very thin (few nm) layer of GBC (the ``pellicle'') overlaid by a 15-45 nm thick layer of CPS (the ``capsule''). AFM-based single-molecule mapping with specific antibody probes shows that CPS is exposed on WT cells, while it is hardly detected on mutant cells impaired in CPS production (ΔcpsE mutant). By contrast, both TEM and AFM show that CPS is over-expressed in mutant cells altered in GBC expression (ΔgbcO mutant), indicating that the production of the two surface glycopolymers is coordinated in WT cells. In addition, AFM topographic imaging and molecular mapping with specific lectin probes demonstrate that removal of CPS (ΔcpsE), but not of GBC (ΔgbcO), leads to the exposure of peptidoglycan, organized into 25 nm wide bands running parallel to the septum. These results indicate that CPS forms a homogeneous barrier protecting the underlying peptidoglycan from environmental exposure, while the presence of GBC does not prevent peptidoglycan detection. This work shows that single-molecule AFM, combined with high-resolution TEM, represents a powerful platform for analysing the molecular arrangement of the cell wall polymers of bacterial pathogens.

  15. Biomechanical implications of excessive endograft protrusion into the aortic arch after thoracic endovascular repair.

    Science.gov (United States)

    Rinaudo, Antonino; Raffa, Giuseppe Maria; Scardulla, Francesco; Pilato, Michele; Scardulla, Cesare; Pasta, Salvatore

    2015-11-01

    Endografts placed in the aorta for thoracic endovascular aortic repair (TEVAR) may determine malappositioning to the lesser curvature of the aortic wall, thus resulting in a devastating complication known as endograft collapse. This premature device failure commonly occurs in young individuals after TEVAR for traumatic aortic injuries as a result of applications outside the physical conditions for which the endograft was designed. In this study, an experimentally-calibrated fluid-structure interaction (FSI) model was developed to assess the hemodynamic and stress/strain distributions acting on the excessive protrusion extension (PE) of endografts deployed in four young patients underwent TEVAR. Endograft infolding was experimentally measured for different hemodynamic scenarios by perfusion testing and then used to numerically calibrate the mechanical behavior of endograft PE. Results evinced that the extent of endograft can severely alter the hemodynamic and structural loads exerted on the endograft PE. Specifically, PE determined a physiological aortic coarctation into the aortic arch characterized by a helical flow in the distal descending aorta. High device displacement and transmural pressure across the stent-graft wall were found for a PE longer than 21 mm. Finally, marked intramural stress and principal strain distributions on the protruded segment of the endograft wall may suggest failure due to material fatigue. These critical parameters may contribute to the endograft collapse observed clinically and can be used to design new devices more suitable for young individuals to be treated with an endoprosthesis for TEVAR of blunt traumatic aortic injuries.

  16. Nonoperative management of pediatric aortic injury with seat belt syndrome.

    Science.gov (United States)

    Parrish, Dan W; Barnhorst, Amanda; Trebska-McGowan, Katarzyna; Amendola, Michael; Haynes, Jeffrey H

    2015-08-01

    "Seat belt syndrome" was first described by Garret and Braunstein in 1962. The syndrome involves skin and abdominal wall ecchymosis (seat belt sign) intra-abdominal solid organ and visceral injuries, as well as Chance fractures (compression and/or wedging deformity of the anterior portion of the vertebral body with disruption or fracture of the posterior elements, generally at L1-L3). We present a case of a 12-year-old male involved in a high-speed motor vehicle collision wearing only a lap belt resulting in seat belt syndrome, with disruption of the abdominal wall, mesenteric avulsion with multiple intestinal perforations, abdominal aortic dissection, and an L2 Chance fracture with cord transection. Intraoperative decision making is outlined with this scenario of complex injuries, and the literature of seat belt syndrome associated with blunt aortic injuries and its management is reviewed.

  17. Transcatheter Aortic Valve Replacement in Bicuspid Aortic Valve Disease

    DEFF Research Database (Denmark)

    Mylotte, Darren; Lefevre, Thierry; Søndergaard, Lars

    2014-01-01

    BACKGROUND: Limited information exists describing the results of transcatheter aortic valve (TAV) replacement in patients with bicuspid aortic valve (BAV) disease (TAV-in-BAV). OBJECTIVES: This study sought to evaluate clinical outcomes of a large cohort of patients undergoing TAV-in-BAV. METHODS...

  18. A Multifrequency Radar System for Detecting Humans and Characterizing Human Activities for Short-Range Through-Wall and Long-Range Foliage Penetration Applications

    Directory of Open Access Journals (Sweden)

    Ram M. Narayanan

    2014-01-01

    Full Text Available A multifrequency radar system for detecting humans and classifying their activities at short and long ranges is described. The short-range radar system operates within the S-Band frequency range for through-wall applications at distances of up to 3 m. It utilizes two separate waveforms which are selected via switching: a wide-band noise waveform or a continuous single tone. The long-range radar system operating in the W-Band millimeter-wave frequency range performs at distances of up to about 100 m in free space and up to about 30 m through light foliage. It employs a composite multimodal signal consisting of two waveforms, a wide-band noise waveform and an embedded single tone, which are summed and transmitted simultaneously. Matched filtering of the received and transmitted noise signals is performed to detect targets with high-range resolution, whereas the received single tone signal is used for the Doppler analysis. Doppler measurements are used to distinguish between different human movements and gestures using the characteristic micro-Doppler signals. Our measurements establish the ability of this system to detect and range humans and distinguish between different human movements at different ranges.

  19. Giant Aortic Pseudoaneurysm with Stanford Type A Aortic Dissection after Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Mertay Boran

    2012-01-01

    Full Text Available Giant pseudoaneurysm of the ascending aorta is a rare but dreadful complication occurring several months or years after aortic surgery. Thoracic aortic aneurysms tend to be asymptomatic and were previously often diagnosed only after a complication such as dissection or rupture. We present a rare case of giant ascending aneurysm with Stanford type A aortic dissection occurring 6 years after aortic valve replacement and also illustrate the potential dimensions the ascending aorta may reach by a pseudoaneurysm and dissection after AVR.

  20. Aortic root geometry in aortic stenosis patients (a SEAS substudy)

    DEFF Research Database (Denmark)

    Bahlmann, Edda; Nienaber, Christoph A; Cramariuc, Dana

    2011-01-01

    AIMS: To report aortic root geometry by echocardiography in a large population of healthy, asymptomatic aortic stenosis (AS) patients in relation to current vendor-specified requirements for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Baseline data in 1481 patients...... with asymptomatic AS (mean age 67 years, 39% women) in the Simvastatin Ezetimibe in AS study were used. The inner aortic diameter was measured at four levels: annulus, sinus of Valsalva, sinotubular junction and supracoronary, and sinus height as the annulo-junctional distance. Analyses were based on vendor......-specified requirements for the aortic root geometry for current available prostheses, CoreValve and Edwards-Sapien. The ratio of sinus of Valsalva height to sinus width was 1:2. In multivariate linear regression analysis, larger sinus of Valsalva height was associated with older age, larger sinus of Valsalva diameter...

  1. Mechanical characterization of human aortas from pressurization testing and a paradigm shift for circumferential residual stress.

    Science.gov (United States)

    Labrosse, Michel R; Gerson, Eleanor R; Veinot, John P; Beller, Carsten J

    2013-01-01

    Material properties needed for accurate stress analysis of the human aorta are still incompletely known, especially as many reports have ignored the presence of residual stresses in the aortic wall. To contribute new material regarding these issues, we carried out measurements and pressurization testing on ascending, thoracic and abdominal aortic samples from 24 human subjects aged 38-77 years, and evaluated the opening angle describing the circumferential residual stress level present in the aorta. We determined material constants for the aorta by gender, anatomic location and age group, according to a simple phenomenological constitutive model. The unpressurized aortic radius positively correlated with age, and the circumferential and longitudinal stretch ratios under systemic pressure negatively correlated with age, confirming the known enlargement and stiffening of the aorta with aging. The opening angle was measured to range from a minimum of 89° to above 360° for extreme cases. For given aortic dimensions and material properties, analysis of the in vivo circumferential and longitudinal mural stress distributions indicated a profound influence of the opening angle. For instance, in the thoracic aorta of males aged 38-66, opening angles in the range of 0° to 80° (resp. 60°) may equalize the gradient of in vivo circumferential (resp. longitudinal) stress between the inner and outer layers of the aorta, as commonly expected; however, opening angles above 160° (resp. 120°) may cause the gradient of circumferential (resp. longitudinal) stress to reverse and increase compared to the case without residual stress, putting the maximum stresses toward the adventitia instead of the intima. Even though the analysis of the aortic wall excluded possible longitudinal residual stresses as well as material inhomogeneities, such as constitutive differences between the intimal, medial and adventitial layers, the experimental data reported herein are important to aortic

  2. A Model for Measured Traveling Waves at End-Diastole in Human Heart Wall by Ultrasonic Imaging Method

    Science.gov (United States)

    Bekki, Naoaki; Shintani, Seine A.; Ishiwata, Shin'ichi; Kanai, Hiroshi

    2016-04-01

    We observe traveling waves, measured by the ultrasonic noninvasive imaging method, in a longitudinal beam direction from the apex to the base side on the interventricular septum (IVS) during the period from the end-diastole to the beginning of systole for a healthy human heart wall. We present a possible phenomenological model to explain part of one-dimensional cardiac behaviors for the observed traveling waves around the time of R-wave of echocardiography (ECG) in the human heart. Although the observed two-dimensional patterns of traveling waves are extremely complex and no one knows yet the exact solutions for the traveling homoclinic plane wave in the one-dimensional complex Ginzburg-Landau equation (CGLE), we numerically find that part of the one-dimensional homoclinic dynamics of the phase and amplitude patterns in the observed traveling waves is similar to that of the numerical homoclinic plane-wave solutions in the CGLE with periodic boundary condition in a certain parameter space. It is suggested that part of the cardiac dynamics of the traveling waves on the IVS can be qualitatively described by the CGLE model as a paradigm for understanding biophysical nonlinear phenomena.

  3. Association of Ficolin-3 with abdominal aortic aneurysm presence and progression

    DEFF Research Database (Denmark)

    Fernandez-García, Carlos-Ernesto; Burillo, Elena; Lindholt, Jes S

    2017-01-01

    BACKGROUND: Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. OBJECTIVES: To define extrahepatic sources...... from healthy tissue. Moreover, ficolin-3 mRNA levels in AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, while little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA...... patients' plasma (n=478) compared with control plasma (n=176), which persisted after adjustment for risk factors [Adj. OR=5.29 (95% CI.:3.27;8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho=0.25) and need for surgical repair was observed, also after adjustment for potential...

  4. Prediction of the evolution of the aortic diameter according to the thrombus signal from MR images on small abdominal aortic aneurysms

    Directory of Open Access Journals (Sweden)

    A. Mutiara

    2011-03-01

    Full Text Available We have studied T1 and T2 weighted MR images of thrombus from examination of patients with small abdominal aortic aneurysms in order to know whether the thrombus signal can be linked with the aortic diameter enlargement, and then could predict rupture risk of the aorta wall. Data were obtained from 16 patients with Small Abdominal Aortic Aneurysms (SAAA who had been examined since July 2006 to January 2010 with MR Images.Several parameters were used to study the thrombus signal, such as mean, median, standard deviation, skewness and kurtosis. Each parameter was calculated for the thrombus area, and the signal in the muscle was used to normalize the mean, median and standard deviation of signal in thrombus. After then, those parameters were compared with evolution of the aortic diameter.13 of the 16 patient with SAAA had a thrombus. Unfortunately there were no correlations between thrombus signals with the evolution of the aortic diameter (R often less then 0.3. But some parameter show links between thrombus signal and maximum diameter (mean (R=0.318, median (R=0.318, skewness (R=0.304 or with D maximum diameter (mean (R=0.512.We cannot use thrombus signal alone as the parameter to predict the evolution of the aortic diameter. This study is the first step of our overall study. In the next step, we will use blood flow velocity with 3D/4D modelisation on the aortic aneurysm as a comparison parameter for predicting the rupture risk of the aortic wall. Moreover, relationship between flow data and thrombus will be studied.

  5. Aortic endothelial cells regulate proliferation of human monocytes in vitro via a mechanism synergistic with macrophage colony-stimulating factor. Convergence at the cyclin E/p27(Kip1) regulatory checkpoint.

    Science.gov (United States)

    Antonov, A S; Munn, D H; Kolodgie, F D; Virmani, R; Gerrity, R G

    1997-06-15

    Monocyte-derived macrophages (Mphis) are pivotal participants in the pathogenesis of atherosclerosis. Evidence from both animal and human plaques indicates that local proliferation may contribute to accumulation of lesion Mphis, and the major Mphi growth factor, macrophage colony stimulating factor (MCSF), is present in atherosclerotic plaques. However, most in vitro studies have failed to demonstrate that human monocytes/Mphis possess significant proliferative capacity. We now report that, although human monocytes cultured in isolation showed only limited MCSF-induced proliferation, monocytes cocultured with aortic endothelial cells at identical MCSF concentrations underwent enhanced (up to 40-fold) and prolonged (21 d) proliferation. In contrast with monocytes in isolation, this was optimal at low seeding densities, required endothelial cell contact, and could not be reproduced by coculture with smooth muscle cells. Intimal Mphi isolated from human aortas likewise showed endothelial cell contact-dependent, MCSF-induced proliferation. Consistent with a two-signal mechanism governing Mphi proliferation, the cell cycle regulatory protein, cyclin E, was rapidly upregulated by endothelial cell contact in an MCSFindependent fashion, but MCSF was required for successful downregulation of the cell cycle inhibitory protein p27(Kip1) before cell cycling. Thus endothelial cells and MCSF differentially and synergistically regulate two Mphi genes critical for progression through the cell cycle.

  6. Reference Values for Cardiac and Aortic Magnetic Resonance Imaging in Healthy, Young Caucasian Adults

    Science.gov (United States)

    Eikendal, Anouk L. M.; Bots, Michiel L.; Haaring, Cees; Saam, Tobias; van der Geest, Rob J.; Westenberg, Jos J. M.; den Ruijter, Hester M.; Hoefer, Imo E.; Leiner, Tim

    2016-01-01

    Background Reference values for morphological and functional parameters of the cardiovascular system in early life are relevant since they may help to identify young adults who fall outside the physiological range of arterial and cardiac ageing. This study provides age and sex specific reference values for aortic wall characteristics, cardiac function parameters and aortic pulse wave velocity (PWV) in a population-based sample of healthy, young adults using magnetic resonance (MR) imaging. Materials and Methods In 131 randomly selected healthy, young adults aged between 25 and 35 years (mean age 31.8 years, 63 men) of the general-population based Atherosclerosis-Monitoring-and-Biomarker-measurements-In-The-YOuNg (AMBITYON) study, descending thoracic aortic dimensions and wall thickness, thoracic aortic PWV and cardiac function parameters were measured using a 3.0T MR-system. Age and sex specific reference values were generated using dedicated software. Differences in reference values between two age groups (25–30 and 30–35 years) and both sexes were tested. Results Aortic diameters and areas were higher in the older age group (all p<0.007). Moreover, aortic dimensions, left ventricular mass, left and right ventricular volumes and cardiac output were lower in women than in men (all p<0.001). For mean and maximum aortic wall thickness, left and right ejection fraction and aortic PWV we did not observe a significant age or sex effect. Conclusion This study provides age and sex specific reference values for cardiovascular MR parameters in healthy, young Caucasian adults. These may aid in MR guided pre-clinical identification of young adults who fall outside the physiological range of arterial and cardiac ageing. PMID:27732640

  7. Characterization of cell wall lipids from the pathogenic phase of Paracoccidioides brasiliensis cultivated in the presence or absence of human plasma.

    Directory of Open Access Journals (Sweden)

    Larissa V G Longo

    Full Text Available BACKGROUND: The fungal cell wall is a complex and dynamic outer structure. In pathogenic fungi its components interact with the host, determining the infection fate. The present work aimed to characterize cell wall lipids from P. brasiliensis grown in the presence and absence of human plasma. We compared the results from isolates Pb3 and Pb18, which represent different phylogenetic species that evoke distinct patterns of experimental paracoccidioidomycosis. METHODOLOGY/PRINCIPAL FINDINGS: We comparatively characterized cell wall phospholipids, fatty acids, sterols, and neutral glycolipids by using both electrospray ionization- and gas chromatography-mass spectrometry analyses of lipids extracted with organic solvents followed by fractionation in silica-gel-60. We detected 49 phospholipid species in Pb3 and 38 in Pb18, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and phosphatidic acid. In both Pb3 and Pb18, PC and PE had the most numerous species. Among the fatty acids, C18:1 and C18:2 were the most abundant species in both isolates, although C18:2 was more abundant in Pb18. There was a different effect of plasma supplementation on fatty acids depending on the fungal isolate. The prevalent glycolipid species was Hex-C18:0-OH/d19:2-Cer, although other four minor species were also detected. The most abundant sterol in all samples was brassicasterol. Distinct profiles of cell wall and total yeast sterols suggested that the preparations were enriched for cell wall components. The presence of plasma in the culture medium specially increased cell wall brassicasterol abundance and also other lipids. CONCLUSIONS/SIGNIFICANCE: We here report an original comparative lipidomic analysis of P. brasiliensis cell wall. Our results open doors to understanding the role of cell wall lipids in fungal biology, and interaction with anti-fungal drugs and the host.

  8. Expression and significance of the expression of monocyte chemoattractant protein-1, insulin like growth factor I, and matrix metalloproteinase-9 in human abdominal aortic aneurysm%单核巨噬细胞趋化因子1、胰岛素样生长因子Ⅰ和基质金属蛋白酶9在人腹主动脉瘤中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    张蓉; 胡明; 费宇行; 李晶; 张沂

    2011-01-01

    目的 观察单核细胞趋化因子1(MCP-1)、胰岛素样生长因子Ⅰ(IGF-Ⅰ)、基质金属蛋白酶9(MMP-9)在人腹主动脉及腹主动脉瘤中的表达,并探讨其在腹主动脉瘤形成中的病生理作用.方法 2010年6-10月经择期外科手术获取的腹主动脉瘤标本15例,均经常规病理检查证实,采用SP免疫组织化学技术检测IGF-Ⅰ、MCP-1、MMP-9蛋白的表达,并以10例非正常死亡健康成人腹主动脉作为对照,对检测结果进行比较分析.结果 腹主动脉瘤中MCP-1、MMP-9的免疫组化染色强度显著高于对照组(P<0.01),IGF-Ⅰ显著低于对照组(P<0.05).相关性分析显示,腹主动脉瘤组织中IGF-Ⅰ表达与MCP-1、MMP-9呈明显负相关(分别为r=-0.791,P<0.01;r=-0.692,P<0.01),而MCP-1的表达与MMP-9呈明显正相关(r=0.932,P<0.01).结论 IGF-Ⅰ表达减少可能会增加主动脉血管壁中层平滑肌细胞的凋亡,或使增殖平衡失调,而平滑肌细凋亡增多可影响细胞外基质正常结构的维持及修复,促进腹主动脉瘤的发生,MCP-1、IGF-Ⅰ、MMP-9三者的表达失衡可能是腹主动脉瘤的发病机制之一.%Objective To observe the expression of monocyte chemoattractant protein-1 (MCP-1), insulin like growth factor I (IGFI) and matrix metalloproteinase-9 (MMP-9) in the local tissue of human abdominal aorta and abdominal aortic aneurysm, and explore their physiopathological role in the pathogenesis of abdominal aortic aneurysm. Methods The specimens were obtained from 15 patients who underwent elective surgical procedures from June to October in 2010, and its pathology was confirmed by routine pathological examination.The expressions of MCP-1, IGF- I and MMP-9 were determined with SP immunohistochemistry method. Specimens of 10 normal human abdominal aortae were used as control and the results were compared with those of abdominal aortic aneurysm. Results The expressions of MCP-1 and MMP-9 in abdominal aortic aneurysm were

  9. Seatbelt triad: severe abdominal wall disruption, hollow viscus injury, and major vascular injury.

    Science.gov (United States)

    Kulvatunyou, Narong; Albrecht, Roxie M; Bender, Jeffrey S; Friese, Randy S; Joseph, Bellal; Latifi, Rifat; O'Keefe, Terrance; Wynn, Julie L; Rhee, Peter M

    2011-05-01

    The triad of seatbelt-related severe abdominal wall disruption, hollow viscus injury, and distal abdominal aortic injury after a motor vehicle collision is uncommon. We present a small case series involving those three clinical features with the goal of preventing a future missed diagnosis of the distal abdominal aortic injury in particular.

  10. Abdominal aortic aneurysm surgery

    DEFF Research Database (Denmark)

    Gefke, K; Schroeder, T V; Thisted, B

    1994-01-01

    The goal of this study was to identify patients who need longer care in the ICU (more than 48 hours) following abdominal aortic aneurysm (AAA) surgery and to evaluate the influence of perioperative complications on short- and long-term survival and quality of life. AAA surgery was performed in 553......, 78% stated that their quality of life had improved or was unchanged after surgery and had resumed working. These data justify a therapeutically aggressive approach, including ICU therapy following AAA surgery, despite failure of one or more organ systems....

  11. Sensitive immunoassay of human chorionic gonadotrophin based on multi-walled carbon nanotube-chitosan matrix.

    Science.gov (United States)

    Li, Na; Yuan, Ruo; Chai, Yaqin; Chen, Shihong; An, Haizhen

    2008-10-01

    A novel amperometric immunosensor for human chorionic gonadotropin (HCG) assay has been fabricated through incorporating toluidine blue (TB) and hemoglobin (Hb) on the multiwall carbon nanotube (MWNT)-chitosan (CS) modified glassy carbon electrode, followed by electrostatic adsorption of a conducting gold nanoparticles (nanogold) film as sensing interface. The MWNT-CS matrix provided a congenial microenvironment for the immobilization of biomolecules and promoted the electron transfer to enhance the sensitivity of the immunosensor. Due to the strong electrocatalytic properties of Hb and MWNT toward H(2)O(2), the Hb and MWNT significantly amplified the current signal of the antigen-antibody reaction. The immobilized toluidine blue as an electron transfer mediator exhibited excellent electrochemical redox property. After the immunosensor was incubated with HCG solution, the access of activity center of the Hb to toluidine blue was partly inhibited, which leaded to a linear decrease in the catalytic efficiency of the Hb to the oxidation of immobilized toluidine blue by H(2)O(2) over HCG concentration ranges from 0.8 to 500 mIU/mL. Under optimal condition, the detection limit for the HCG immunoassay was 0.3 mIU/mL estimated at a signal-to-noise ratio of 3. Moreover, the proposed immunosensor displayed a satisfactory stability and reproducibility.

  12. Microdissection of Human Esophagogastric Junction Wall with Phase-contrast X-ray CT Imaging

    Science.gov (United States)

    Zhang, Jianfa; Zhou, Guangzhao; Tian, Dongping; Lin, Runhua; Peng, Guanyun; Su, Min

    2015-01-01

    Phase-contrast x-ray imaging using an x-ray interferometer has great potential to reveal the structures inside soft tissues, because the sensitivity of this method to hydrogen, carbon, nitrogen, and oxygen is about 1000 times higher than that of the absorption-contrast x-ray method. In this study, we used phase-contrast X-ray CT to investigate human resected esophagogastric junction. This technology revealed the three-layer structure of the esophagogastric junction wall—mucous, submucosa and muscular layers. The mucous and muscular layers were clearly separated by a loose submucosa layer with a honeycomb appearance. The shape of the mucous and muscular layers was intact. The boundary between the mucous and submucosa layers was distinct, as was the border of the muscular and submucosa layers. The surface of the esophagogastric junction was displayed clearly through 3D reconstruction. The technology might be helpful in the diagnosis of esophagogastric junction lesion, especially for the early adenocarcinoma. PMID:26346099

  13. Detection of antibodies to bacterial cell wall peptidoglycan in human sera. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Heymer, B.; Schleifer, K.H.; Read, S.; Zabriskie, J.B.; Krause, R.M.

    1976-07-01

    A radioimmunoassay has been developed for the measurement of antibodies to peptidoglycan in human sera including patients with rheumatic feaver and juvenile rheumatoid arthritis. The assay is based on the percentage of binding of the hapten /sup 125/I-L-Ala-..gamma..-D-Glu-L-Lys-D-Ala-D-Ala, the major peptide determinant of peptidoglycan. Because of differences in the avidity of the antibodies in different sera, the amount of antibody was expressed as pentapeptide hapten-binding capacity (pentapeptide-HBC in ng/ml of serum). Fourteen out of 105 normal blood donors had a pentapeptide-HBC value greater than or equal to 75 ng/ml serum. Values in healthy children 5 to 18 years of age were less than or equal to 50 ng/ml. Sixty-eight percent of the individuals with rheumatic fever had values greater than or equal to 75 ng/ml, an indication that streptococcal infections can stimulate an immune response to peptidoglycan. Thirty-five percent of the patients with juvenile rheumatoid arthritis had values greater than or equal to 75 ng/ml. Such a finding points to a possible association between bacterial infections and juvenile rheumatoid arthritis.

  14. Markers of inflammation collocate with increased wall stress in human coronary arterial plaque.

    Science.gov (United States)

    Hallow, Karen Melissa; Taylor, W Robert; Rachev, Alexander; Vito, Raymond Peter

    2009-12-01

    In this study, we hypothesized that spatial relationships exist between the local mechanical environment and inflammatory marker expression in atherosclerotic plaques, and that these relationships are plaque-progression dependent. Histologic cross-sections were collected at regular intervals along the length of diseased human coronary arteries and classified as early, intermediate, advanced, or mature based on their morphological features. For each cross-section, the spatial distribution of stress was determined using a 2D heterogeneous finite element model, and the corresponding distribution of selected inflammatory markers (macrophages, matrix metalloproteinase-1 [MMP-1], and nuclear factor-kappa B [NF-κB]) were determined immunohistochemically. We found a monotonic spatial relationship between mechanical stress and activated NF-κB that was consistent in all stages of plaque progression. We also identified progression-dependent relationships between stress and both macrophage presence and MMP-1 expression. These findings add to our understanding of the role of mechanical stress in stimulating the inflammatory response, and help explain how mechanical factors may regulate complex biological changes in remodeling.

  15. Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of severe aortic stenosis

    DEFF Research Database (Denmark)

    Siontis, George C M; Praz, Fabien; Pilgrim, Thomas

    2016-01-01

    AIMS: In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups. METHODS AND RESULTS...

  16. [Aortic valve replacement for the small aortic annulus].

    Science.gov (United States)

    Oshima, H; Usui, A; Akita, T; Ueda, Y

    2006-04-01

    Aortic valve surgery for the small aortic annulus is still challenging for surgeons. Recently, the new types of high performance prosthesis have been developed and the chance of an aortic root enlargement (ARE) is decreasing. In this study, we propose the ideal strategy of the aortic surgery for the small aortic annulus. We analyzed the clinical records of 158 patients who underwent aortic valve replacement from August 1999 to October 2005 in our institution. The small aortic annulus was observed in 38 patients (24%). Fourteen patients of this group underwent ARE. Patient-prosthesis mismatch (PPM) was less frequently observed in patients with ARE compared to those without ARE. The additional time required for ARE was not considerable, and neither ischemic time nor cardiopulmonary bypass time was significantly prolonged by ARE. In conclusion, we have to select a prosthesis with sufficient orifice area to avoid PPM, otherwise we should choose an option of ARE. For this consideration, we definitely need the chart that demonstrates the relationship between the nominal size of various types of prostheses and the size of a patient's annulus that those prostheses actually fit.

  17. Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, Raoul [University Medical Center Heidelberg, Department of Congenital Heart Disease and Pediatric Cardiology, Heidelberg (Germany); Neu, Marie [University Medical Center, Department of Pediatric Hematology/Oncology/Hemostaseology, Mainz (Germany); Hirtler, Daniel [University of Freiburg, Department of Congenital Heart Defects and Pediatric Cardiology, Heart Center, Freiburg im Breisgau (Germany); Gimpel, Charlotte [Center for Pediatrics, Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Freiburg im Breisgau (Germany); Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Geiger, Julia [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); University Children' s Hospital, Department of Radiology, Zuerich (Switzerland)

    2017-04-15

    Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections. (orig.)

  18. Balloon aortic valvuloplasty as a bridge to aortic valve replacement in a patient with severe calcific aortic stenosis.

    Science.gov (United States)

    Swinkels, B M; Jaarsma, W; Wely, L Relik-van; van Swieten, H A; Ernst, J M P G; Plokker, H W M

    2003-03-01

    This case report describes a patient with severe calcific aortic stenosis who was initially considered inoperable because of a very poor left ventricular function and severe pulmonary hypertension. After balloon aortic valvuloplasty, the clinical and haemodynamic status of the patient improved to such an extent that subsequent aortic valve replacement was considered possible and eventually proved to be successful. Balloon aortic valvuloplasty has value as a potential bridge to aortic valve replacement when the risks for surgery are considered to be too high.

  19. Valve-sparing aortic root replacement and aortic valve repair in a patient with acromegaly and aortic root dilatation

    Directory of Open Access Journals (Sweden)

    Karel Van Praet

    2015-07-01

    Full Text Available Aortic regurgitation and dilatation of the aortic root and ascending aorta are severe complications of acromegaly. The current trend for management of an aortic root aneurysm is valve-sparing root replacement as well as restoring the diameter of the aortic sinotubular junction (STJ and annulus. Our case report supports the recommendation that in patients with acromegaly, severe aortic root involvement may indicate the need for surgery.

  20. Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD)

    National Research Council Canada - National Science Library

    Pape, Linda A; Tsai, Thomas T; Isselbacher, Eric M; Oh, Jae K; O'gara, Patrick T; Evangelista, Arturo; Fattori, Rossella; Meinhardt, Gabriel; Trimarchi, Santi; Bossone, Eduardo; Suzuki, Toru; Cooper, Jeanna V; Froehlich, James B; Nienaber, Christoph A; Eagle, Kim A

    2007-01-01

    .... However, few studies of acute aortic dissection patients and aortic size exist. We used data from our registry of acute aortic dissection patients to better understand the relationship between aortic diameter and type A dissection...

  1. High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes.

    Science.gov (United States)

    Falcón, Rocío; Martínez, Alba; Albert, Eliseo; Madrid, Silvia; Oltra, Rosa; Giménez, Estela; Soriano, Mario; Vinuesa, Víctor; Gozalbo, Daniel; Gil, María Luisa; Navarro, David

    2016-05-01

    Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index 70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes.

  2. Gender differences in experimental aortic aneurysm formation.

    Science.gov (United States)

    Ailawadi, Gorav; Eliason, Jonathan L; Roelofs, Karen J; Sinha, Indranil; Hannawa, Kevin K; Kaldjian, Eric P; Lu, Guanyi; Henke, Peter K; Stanley, James C; Weiss, Stephen J; Thompson, Robert W; Upchurch, Gilbert R

    2004-11-01

    It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs). Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase. These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.

  3. Reinforced aortic root reconstruction for acute type A aortic dissection involving the aortic root

    Directory of Open Access Journals (Sweden)

    Han Qing-qi

    2013-06-01

    Full Text Available OBJECTIVE: There are debates regarding the optimal approach for AAAD involving the aortic root. We described a modified reinforced aortic root reconstruction approach for treating AAAD involving the aortic root. METHODS: A total of 161 patients with AAAD involving the aortic root were treated by our modified reinforced aortic root reconstruction approach from January 1998 to December 2008. Key features of our modified approach were placement of an autologous pericardial patch in the false lumen, lining of the sinotubular junction lumen with a polyester vascular ring, and wrapping of the vessel with Teflon strips. Outcome measures included post-operative mortality, survival, complications, and level of aortic regurgitation. RESULTS: A total of 161 patients were included in the study (mean age: 43.3 1 15.5 years. The mean duration of follow-up was 5.1 1 2.96 years (2-12 years. A total of 10 (6.2% and 11 (6.8% patients died during hospitalization and during follow-up, respectively. Thirty-one (19.3% patients experienced postoperative complications. The 1-, 3-, 5-, and 10-year survival rates were 99.3%, 98%, 93.8%, and 75.5%, respectively. There were no instances of recurrent aortic dissection, aortic aneurysm, or pseudoaneurysm during the entire study period. The severity of aortic regurgitation dramatically decreased immediately after surgery (from 28.6% to 0% grade 3-4 and thereafter slightly increased (from 0% to 7.2% at 5 years and 9.1% at 10 years. CONCLUSION: This modified reinforced aortic root reconstruction was feasible, safe and durable/effective, as indicated by its low mortality, low postoperative complications and high survival rate.

  4. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    Science.gov (United States)

    Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

    2014-11-01

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml-1 with a limit of detection of 0.16 ng ml-1.

  5. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Swati; Kumar, Ashok, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007 (India); Academy of Scientific and Innovative Research (AcSIR), New Delhi (India); Khare, Shashi [National Centre for Disease Control, Sham Nath Marg, Delhi 110054 (India); Mulchandani, Ashok [Department of Chemical and Environmental Engineering, University of California, Riverside, California 92521 (United States); Rajesh, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012 (India)

    2014-11-24

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml{sup −1} with a limit of detection of 0.16 ng ml{sup −1}.

  6. Non-covalent attachment of silver nanoclusters onto single-walled carbon nanotubes with human serum albumin as linking molecule

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez-Galván, Andrés, E-mail: andres.rodriguez@nucleares.unam.mx [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Instituto de Física, Dpto. Física Experimental, Universidad Nacional Autónoma de México, Coyoacán, México, DF 04510 (Mexico); Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, México, DF 14080 (Mexico); Heredia, Alejandro [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Amelines-Sarria, Oscar; Rivera, Margarita [Instituto de Física, Dpto. Materia Condensada, Universidad Nacional Autónoma de México, Coyoacán, 04510 México D.F. (Mexico); and others

    2015-03-15

    The attachment of silver nanoclusters (AgNCs) onto single-walled carbon nanotubes (SWNTs) for the formation of integrated fluorescence sites has attracted much attention due their potential applications as biological probes and nanovectors in theragnosis. Here, we report the preparation through assembly of fluorescent quasi 1-D nanomaterial based on SWNTs and silver nanoclusters (AgNCs) non-covalently attached to human serum albumin as biological linker. The fluorescent SWNT–AgNCs–HSA conjugates were characterized by atomic force microscopy, high-resolution transmission electron microscopy (HRTEM), high angle annular dark field scanning TEM (HAADF-STEM), fluorescent and UV–vis spectroscopy. The above techniques confirmed that AgNCs were non-covalently attached onto the external surface of SWNTs. In addition, it was observed that the modification did not affect the optical properties of the synthesized AgNCs since the absorption spectra and fluorescence under UV irradiation (λ = 365 nm) remain the same. The effect of the functionalized systems was tested on mammal red blood cells (RBCs) and it was found that their structural integrity was compromised by the conjugates, limiting their biological and medical applications.

  7. Thin films of single-walled carbon nanotubes promote human osteoblastic cells (Saos-2) proliferation in low serum concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Akasaka, Tsukasa, E-mail: akasaka@den.hokudai.ac.jp [Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7, Kita-ku, Sapporo, 060-8586 (Japan); Yokoyama, Atsuro; Matsuoka, Makoto [Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7, Kita-ku, Sapporo, 060-8586 (Japan); Hashimoto, Takeshi [Meijo Nano Carbon Co., Ltd., Otsubashi Bldg. 4F, 3-4-10, Marunouchi, Naka-ku, Nagoya, 460-0002 (Japan); Watari, Fumio [Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7, Kita-ku, Sapporo, 060-8586 (Japan)

    2010-04-06

    One strategy used for the regeneration of bone is the development of cell culture substrates and scaffolds that can control osteoblast proliferation and differentiation. In recent investigations, carbon nanotubes (CNTs) have been utilized as scaffolds for osteoblastic cell cultures; however, there are only a few reports describing the proliferation of osteoblastic cells on thin CNT films; in particular, the effects of serum concentration on cell proliferation have not been studied. In the present study, we prepared culture dishes with homogeneous thin or thick films of non-modified CNTs and examined the effect of serum concentrations on human osteoblastic cells (Saos-2) proliferation in these culture dishes. We demonstrated that the ratio of cell proliferation was strongly affected by the concentration of serum. Interestingly, single-walled carbon nanotube (SWNT) thin films were found to be the most effective substrate for the proliferation of Saos-2 cells in low concentrations of serum. Thus, thin SWNT films may be used as an effective biomaterial for the culture of Saos-2 cells in low serum concentrations.

  8. Binding of Human GII.4 Norovirus Virus-Like Particles to Carbohydrates of Romaine Lettuce Leaf Cell Wall Materials

    Science.gov (United States)

    Esseili, Malak A.

    2012-01-01

    Norovirus (NoV) genogroup II genotype 4 (GII.4) strains are the dominant cause of the majority of food-borne outbreaks, including those that involve leafy greens, such as lettuce. Since human NoVs use carbohydrates of histo-blood group antigens as receptors/coreceptors, we examined the role of carbohydrates in the attachment of NoV to lettuce leaves by using virus-like particles (VLPs) of a human NoV/GII.4 strain. Immunofluorescence analysis showed that the VLPs attached to the leaf surface, especially to cut edges, stomata, and along minor veins. Binding was quantified using enzyme-linked immunosorbent assay (ELISA) performed on cell wall materials (CWM) from innermost younger leaves and outermost lamina of older leaves. The binding to CWM of older leaves was significantly (P carbohydrates of CWM or porcine gastric mucin (PGM) (a carbohydrate control) using 100 mM sodium periodate (NaIO4) significantly decreased the binding an average of 17% in younger leaves, 43% in older leaves, and 92% for PGM. In addition, lectins recognizing GalNAc, GlcNAc, and sialic acid at 100 μg/ml significantly decreased the binding an average of 41%, 33%, and 20% on CWM of older leaves but had no effect on younger leaves. Lectins recognizing α-d-Gal, α-d-Man/α-d-Glc, and α-l-Fuc showed significant inhibition on CWM of older leaves as well as that of younger leaves. All lectins, except for the lectin recognizing α-d-Gal, significantly inhibited NoV VLP binding to PGM. Collectively, our results indicate that NoV VLPs bind to lettuce CWM by utilizing multiple carbohydrate moieties. This binding may enhance virus persistence on the leaf surface and prevent effective decontamination. PMID:22138991

  9. A mathematical model of aortic aneurysm formation

    Science.gov (United States)

    Hao, Wenrui; Gong, Shihua; Wu, Shuonan; Xu, Jinchao; Go, Michael R.; Friedman, Avner; Zhu, Dai

    2017-01-01

    Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material. PMID:28212412

  10. Blood flow characteristics in the aortic arch

    Science.gov (United States)

    Prahl Wittberg, Lisa; van Wyk, Stevin; Mihaiescu, Mihai; Fuchs, Laszlo; Gutmark, Ephraim; Backeljauw, Philippe; Gutmark-Little, Iris

    2012-11-01

    The purpose with this study is to investigate the flow characteristics of blood in the aortic arch. Cardiovascular diseases are associated with specific locations in the arterial tree. Considering atherogenesis, it is claimed that the Wall Shear Stress (WSS) along with its temporal and spatial gradients play an important role in the development of the disease. The WSS is determined by the local flow characteristics, that in turn depends on the geometry as well as the rheological properties of blood. In this numerical work, the time dependent fluid flow during the entire cardiac cycle is fully resolved. The Quemada model is applied to account for the non-Newtonian properties of blood, an empirical model valid for different Red Blood Cell loading. Data obtained through Cardiac Magnetic Resonance Imaging have been used in order to reconstruct geometries of the the aortic arch. Here, three different geometries are studied out of which two display malformations that can be found in patients having the genetic disorder Turner's syndrome. The simulations show a highly complex flow with regions of secondary flow that is enhanced for the diseased aortas. The financial support from the Swedish Research Council (VR) and the Sweden-America Foundation is gratefully acknowledged.

  11. An Important but Forgotten Technique: Aortic Fenestration.

    Science.gov (United States)

    Yalcin, Mihriban; Tayfur, Kaptan Derya; Urkmez, Melih

    2016-10-01

    Aortic fenestration is a technique that treats organ ischemia in descending aortic dissection. Open surgical aortic fenestration is an effective yet uncommonly used and widely forgotten procedure. Here, we describe 2 patients suffering from chronic thoracoabdominal aortic dissection, and we aimed to identify under what circumstances surgical aortic fenestration should be applied, to assess its safety and efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. [Role of computational fluid dynamics in thoracic aortic diseases research: technical superiority and application prospect].

    Science.gov (United States)

    Li, Weihao; Shen, Chenyang; Zhang, Xiaoming; Zhang, Tao

    2015-08-01

    Computational fluid dynamics (CFD) technology has the potential to simulate normal or pathologic aortic blood flow changes of mechanical properties and flow field, thereby helping researchers understand and reveal the occurrence, development and prognosis of aortic disease. In aortic diseases research, the initial conditions of CFD numerical simulation has experienced a developed process from idealization (forward engineering), rigid vessel wall, uniform cross-sections, laminar flow and stable blood flow towards personalization (reverse engineering), elastic vessel wall (fluid-solid coupling technique), cone-shaped diminishing cross-sections, turbulent flow, pulsatile blood flow. In this review, the research status, the technical superiority and application prospect of CFD technology were discussed with examples in following three major application areas: (1) dynamics characteristic and mechanical properties in normal thoracic aorta; (2) occurrence, advance and disruptive risk predicting in thoracic aortic aneurysm; (3) therapeutic effect and aneurysmal dilatation simulation in thoracic aortic dissection. For the future, the CFD technology may profoundly put an influence on the awareness to aortic diseases and treatment strategies.

  13. Nitrative DNA damage induced by multi-walled carbon nanotube via endocytosis in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Feiye, E-mail: zhizi0269@doc.medic.mie-u.ac.jp [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507 (Japan); Ma, Ning, E-mail: maning@suzuka-u.ac.jp [Faculty of Health Science, Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka, Mie, 510-0293 (Japan); Horibe, Yoshiteru, E-mail: violinteru@yahoo.co.jp [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507 (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minami-Tamagaki-cho, Suzuka, Mie, 513-8670 (Japan); Murata, Mariko, E-mail: mmurata@doc.medic.mie-u.ac.jp [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507 (Japan); Hiraku, Yusuke, E-mail: y-hiraku@doc.medic.mie-u.ac.jp [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507 (Japan)

    2012-04-15

    Carbon nanotube (CNT) has a promising usage in the field of material science for industrial purposes because of its unique physicochemical property. However, intraperitoneal administration of CNT was reported to cause mesothelioma in experimental animals. Chronic inflammation may contribute to carcinogenesis induced by fibrous materials. 8-Nitroguanine is a mutagenic DNA lesion formed during inflammation and may play a role in CNT-induced carcinogenesis. In this study, we examined 8-nitroguanine formation in A549 human lung alveolar epithelial cells treated with multi-walled CNT (MWCNT) by fluorescent immunocytochemistry. Both MWCNTs with diameter of 20–30 nm (CNT20) and 40–70 nm (CNT40) significantly induced 8-nitroguanine formation at 5 and 10 μg/ml (p < 0.05), which persisted for 24 h, although there was no significant difference in DNA-damaging abilities of these MWCNTs. MWCNTs significantly induced the expression of inducible nitric oxide synthase (iNOS) for 24 h (p < 0.05). MWCNTs also significantly increased the level of nitrite, a hydrolysis product of oxidized NO, in the culture supernatant at 4 and 8 h (p < 0.05). MWCNT-induced 8-nitroguanine formation and iNOS expression were largely suppressed by inhibitors of iNOS (1400 W), nuclear factor-κB (Bay11-7082), actin polymerization (cytochalasin D), caveolae-mediated endocytosis (methyl-β-cyclodextrin, MBCD) and clathrin-mediated endocytosis (monodansylcadaverine, MDC). Electron microscopy revealed that MWCNT was mainly located in vesicular structures in the cytoplasm, and its cellular internalization was reduced by MBCD and MDC. These results suggest that MWCNT is internalized into cells via clathrin- and caveolae-mediated endocytosis, leading to inflammatory reactions including iNOS expression and resulting nitrative DNA damage, which may contribute to carcinogenesis. Highlights: ►Multi-walled carbon nanotube (MWCNT) caused DNA damage in A549 cells. ►MWCNT formed 8-nitroguanine, a DNA lesion

  14. Finite element model determination of correction factors used for measurement of aortic diameter via conductance.

    Science.gov (United States)

    Hettrick, D A; Battocletti, J; Ackmann, J; Warltier, D C

    1999-01-01

    Traditional methods for estimating the slope alpha and offset volume Vp for determining real-time chamber volume by the conductance catheter technique are not suited to measurements made in the aorta due to the relatively low resistivity of the aortic wall. We developed three distinct three-dimensional finite element models of the conductance catheter and surrounding tissues in order to predict alpha and Vp and to examine the nature of the electric field near the aortic wall. A heterogeneous isotropic model of the catheter, aorta and surrounding tissues accurately predicted the values of alpha and Vp. A homogeneous anisotropic model was developed to examine the effects of anisotropy of blood and the layers of the aortic wall on measured values of resistance, alpha and Vp. This model demonstrated that anisotropy of blood and aortic wall tissue can increase the values of both alpha and Vp. Finally, a three-dimensional homogeneous isotropic rectangular model allowed examination of the effects of catheter position. This model showed small effects of catheter position on measured resistance (9.7% increase) and larger effects on alpha (21.2% decrease) and Vp (41.9% increase). We conclude the following: the FEA models may lead to accurate estimate values of alpha and Vp in vivo. The unique anisotropic conductive properties of the layers of the aortic wall contribute to the high observed values of alpha and Vp in the aorta. Finally, catheter position has a proportionately greater effect on alpha and Vp than on measured resistance. The results of this study should assist in the determination of aortic mechanical properties using conductance catheter measurements of vessel dimension.

  15. Histology of a Marfan aorta 4.5 years after personalized external aortic root support.

    Science.gov (United States)

    Pepper, John; Goddard, Martin; Mohiaddin, Raad; Treasure, Tom

    2015-09-01

    In 2008, a 26-year old man had personalized external aortic root support (PEARS) with a macroporous mesh. He was the 16th of 46 patients to have this operation. He had a typical Marfan habitus. His mother died of this disease as did his brother, with an aortic dissection. The patient himself died suddenly 4.5 years after his PEARS operation. At autopsy, there was no blood in the pericardium. The coronary orifices and proximal arteries were normal. His bicuspid aortic valve was minimally regurgitant as it was prior to operation and remained throughout follow-up. Macroscopically the implanted mesh was embedded in the adventitia and not separable from the aortic wall. Microscopically it was fully incorporated with collagen fibres as has been seen in our animal studies. The unsupported aortic arch showed some focal fragmentation of elastic fibres and a mild increase in mucopolysaccharides consistent with Marfan syndrome. These appearances were not present in the supported aortic root, which had the histological appearance of a normal aorta. He was the first patient to die with an implant. The histological appearances suggest the possibility that the incorporated support of the aortic root allowed recovery of the microstructure of the media.

  16. Evaluation of aortic cannula jet lesions in a porcine cardiopulmonary bypass (CPB) model.

    Science.gov (United States)

    Schnürer, C; Hager, M; Györi, G; Velik-Salchner, C; Moser, P L; Laufer, G; Lorenz, I H; Kolbitsch, C

    2011-02-01

    In cardiosurgery patients atherosclerotic debris displaced from the cannulation site but also from the opposite aortic wall by the "sandblast-like" effect of the high-pressure jet emanating from the cannula is a potential source of intraoperative arterial embolization and consequently postoperative neurologic dysfunction. The present study examined the extent to which shear stress exerted on the intact aortic intima by an aortic cannula jet stream can cause endothelial lesions that promote thrombogenesis and consequently thrombembolism. A single-stream, straight-tip aortic cannula was used in a porcine cardiopulmonary bypass (CPB) model. Following a 120-minute CPB pump run, a 60-minute stabilization period was allowed before sacrificing the pigs (N.=40) for histological evaluation of the ascending aorta and the brain. Opposite the cannulation site endothelial lesions (diameter: 3.81±1.3 mm; depth: 0.017±0.003 mm) were present in 22.5% (9/40) of aortic specimens. Cerebral thrombembolic lesions were not found. The present study showed that single-stream, straight-tip aortic cannulas caused jet lesions of the formerly intact aortic endothelium opposite the cannulation site in 22.5% of cases in a porcine CPB model.

  17. Early patency rate and fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms.

    Science.gov (United States)

    Omura, Atsushi; Yamanaka, Katsuhiro; Miyahara, Shunsuke; Sakamoto, Toshihito; Inoue, Takeshi; Okada, Kenji; Okita, Yutaka

    2014-06-01

    The present study analyzes the early patency of intercostal artery reconstruction, using graft interposition and aortic patch anastomosis, and determines the fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms. We selected 115 patients (mean age, 63 ± 15 years; range, 19-83 years; male, n = 83) treated by thoracoabdominal aortic aneurysm repair with 1 or more reconstructed intercostal arteries at the Kobe University Graduate School of Medicine between October 1999 and December 2012. The intercostal arteries were reconstructed using graft interposition (n = 66), aortic patch anastomosis (n = 42), or both (n = 7). The hospital mortality rate was 7.8% (n = 9). Eleven patients (9.6%) developed spinal cord ischemic injury (permanent, n = 6, transient, n = 5). The average number of reconstructed intercostal arteries per patient was 3.0 ± 1.5 (1-7), and 345 intercostal arteries were reattached. The overall patency rate was 74.2% (256/345) and that of aortic patch anastomosis was significantly better than that of graft interposition (90.8% [109/120] vs 65.3% [147/225], P intercostal arteries became dilated in 2 patients. Aortic patch anastomosis might offer better patency rates and prevent spinal cord ischemic injury compared with graft interposition. Although aneurysmal changes in intercostal artery reconstructions are rare, large blocks of aortic wall reconstruction should be closely monitored. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  18. Deficient signaling via Alk2 (Acvr1 leads to bicuspid aortic valve development.

    Directory of Open Access Journals (Sweden)

    Penny S Thomas

    Full Text Available Bicuspid aortic valve (BAV is the most common congenital cardiac anomaly in humans. Despite recent advances, the molecular basis of BAV development is poorly understood. Previously it has been shown that mutations in the Notch1 gene lead to BAV and valve calcification both in human and mice, and mice deficient in Gata5 or its downstream target Nos3 have been shown to display BAVs. Here we show that tissue-specific deletion of the gene encoding Activin Receptor Type I (Alk2 or Acvr1 in the cushion mesenchyme results in formation of aortic valve defects including BAV. These defects are largely due to a failure of normal development of the embryonic aortic valve leaflet precursor cushions in the outflow tract resulting in either a fused right- and non-coronary leaflet, or the presence of only a very small, rudimentary non-coronary leaflet. The surviving adult mutant mice display aortic stenosis with high frequency and occasional aortic valve insufficiency. The thickened aortic valve leaflets in such animals do not show changes in Bmp signaling activity, while Map kinase pathways are activated. Although dysfunction correlated with some pro-osteogenic differences in gene expression, neither calcification nor inflammation were detected in aortic valves of Alk2 mutants with stenosis. We conclude that signaling via Alk2 is required for appropriate aortic valve development in utero, and that defects in this process lead to indirect secondary complications later in life.

  19. Mycotic Saccular Abdominal Aortic Aneurysm in an Infant after Cardiac Catheterization: A Case Report.

    Science.gov (United States)

    Benrashid, Ehsan; McCoy, Christopher C; Rice, Henry E; Shortell, Cynthia K; Cox, Mitchell W

    2015-10-01

    Abdominal aortic aneurysms (AAAs) are a rare entity in the pediatric population. Children with mycotic (infectious) AAA in particular are at risk of life-threatening rupture due to their rapid expansion coupled with aortic wall thinning and deterioration. Here, we present the case of a 10-month-old infant with prior 2-staged repair for hypoplastic left heart syndrome that was incidentally discovered to have a mycotic AAA on abdominal ultrasound (US) for evaluation of renovascular hypertension. Before the time of evaluation with US, the infant had developed methicillin-resistant Staphylococcus aureus bacteremia 3 days after cardiac catheterization with percutaneous thoracic aortic balloon angioplasty. She had normal aortic contours on contrasted computed tomography scan of the abdomen approximately 2 weeks before the aforementioned US evaluation. This infant subsequently underwent open aneurysmorrhaphy with cryopreserved vein patch angioplasty with resolution of her aneurysmal segment. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications

    Science.gov (United States)

    Lecarpentier, E.; Bhatt, M.; Bertin, G. I.; Deloison, B.; Salomon, L. J.; Deloron, P.; Fournier, T.; Barakat, A. I.; Tsatsaris, V.

    2016-01-01

    Introduction In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. Material and Methods To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. Results The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour. Conclusion Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB. PMID:26815115

  1. FUNCTIONAL AORTIC STIFFNESS:ROLE OF CD4+ T LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    Beenish A. Majeed

    2015-08-01

    Full Text Available The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1-/- mice and additionally characterized the component of vascular stiffness due to vasoconstriction versus vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young’s modulus in C57BL/6J mice by 3-fold but caused no change in the RAG 1-/- mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4+ T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1-/- mice. In order to account for the hydraulic versus material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity decreased from 3- to 2-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4+ T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling.

  2. Bicuspid aortic valve hemodynamics: a fluid-structure interaction study

    Science.gov (United States)

    Chandra, Santanu; Seaman, Clara; Sucosky, Philippe

    2011-11-01

    The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV.

  3. In Vivo/Ex Vivo MRI-Based 3D Non-Newtonian FSI Models for Human Atherosclerotic Plaques Compared with Fluid/Wall-Only Models.

    Science.gov (United States)

    Yang, Chun; Tang, Dalin; Yuan, Chun; Hatsukami, Thomas S; Zheng, Jie; Woodard, Pamela K

    2007-01-01

    It has been recognized that fluid-structure interactions (FSI) play an important role in cardiovascular disease initiation and development. However, in vivo MRI multi-component FSI models for human carotid atherosclerotic plaques with bifurcation and quantitative comparisons of FSI models with fluid-only or structure-only models are currently lacking in the literature. A 3D non-Newtonian multi-component FSI model based on in vivo/ex vivo MRI images for human atherosclerotic plaques was introduced to investigate flow and plaque stress/strain behaviors which may be related to plaque progression and rupture. Both artery wall and plaque components were assumed to be hyperelastic, isotropic, incompressible and homogeneous. Blood flow was assumed to be laminar, non-Newtonian, viscous and incompressible. In vivo/ex vivo MRI images were acquired using histologically-validated multi-spectral MRI protocols. The 3D FSI models were solved and results were compared with those from a Newtonian FSI model and wall-only/fluid-only models. A 145% difference in maximum principal stresses (Stress-P(1)) between the FSI and wall-only models and 40% difference in flow maximum shear stress (MSS) between the FSI and fluid-only models were found at the throat of the plaque using a severe plaque sample (70% severity by diameter). Flow maximum shear stress (MSS) from the rigid wall model is much higher (20-40% in maximum MSS values, 100-150% in stagnation region) than those from FSI models.

  4. Abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal

    2010-01-01

    Although the number of elective operations for abdominal aortic aneurysms (AAA) is increasing, the sex- and age-standardised mortality rate of AAAs continues to rise, especially among men aged 65 years or more. The lethality of ruptured AAA continues to be 80-95%, compared with 5-7% by elective...... inhibit further AAA progression. All 4 existing RCTs point in the same direction, viz. in favour of screening of men aged 65 and above. We found that screening significantly reduced AAA-related mortality by 67% within the first five years (NNT = 352). Restriction of screening to men with previous...... year gained was 157 euro [1,170 DKK] and the cost per QALY at 178 euro [1,326 DKK]. In all, the ethical dilemma of the prophylactic operation, and the limited psychological side effects seem not to outweigh the benefits of screening. Conclusively, we found that offering men aged 65-73 years screening...

  5. Morphological and Biomechanical Differences in the Elastase and AngII apoE−/− Rodent Models of Abdominal Aortic Aneurysms

    Directory of Open Access Journals (Sweden)

    Evan H. Phillips

    2015-01-01

    Full Text Available An abdominal aortic aneurysm (AAA is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals have been developed to study the disease during its initiation and progression. To date, most studies have used ex vivo methods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence from in vivo ultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngII apoE−/− mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments.

  6. Transcatheter Aortic Heart Valve Thrombosis

    DEFF Research Database (Denmark)

    Hansson, Nicolaj C; Grove, Erik L; Andersen, Henning R;

    2016-01-01

    BACKGROUND: There is increasing focus on transcatheter heart valve (THV) thrombosis. However, there are limited data on incidence, clinical implications and predisposing factors of THV thrombosis following transcatheter aortic valve replacement (TAVR). OBJECTIVES: We assessed the incidence...

  7. Adult thoracic and abdominal aortic

    Directory of Open Access Journals (Sweden)

    Randa O. Kaddah

    2016-06-01

    Conclusion: Aortic COA could be found in any segment of the aorta. Proper identification of the anatomical details and pressure gradient studies are important factors affecting the plan of management.

  8. CONGENITAL QUADRICUSPID AORTIC-VALVE

    NARCIS (Netherlands)

    BROUWER, MHJ; DEGRAAF, JJ; EBELS, T

    1993-01-01

    Two patients with a quadricuspid aortic valve are described, one of them with concomitant juxtaposed coronary orifices facing the right hand facing sinus. The etiology and incidence of this congenital anomaly will be discussed.

  9. Minimally invasive aortic valve replacement

    DEFF Research Database (Denmark)

    Foghsgaard, Signe; Schmidt, Thomas Andersen; Kjaergard, Henrik K

    2009-01-01

    In this descriptive prospective study, we evaluate the outcomes of surgery in 98 patients who were scheduled to undergo minimally invasive aortic valve replacement. These patients were compared with a group of 50 patients who underwent scheduled aortic valve replacement through a full sternotomy....... The 30-day mortality rate for the 98 patients was zero, although 14 of the 98 mini-sternotomies had to be converted to complete sternotomies intraoperatively due to technical problems. Such conversion doubled the operative time over that of the planned full sternotomies. In the group of patients whose...... is an excellent operation in selected patients, but its true advantages over conventional aortic valve replacement (other than a smaller scar) await evaluation by means of randomized clinical trial. The "extended mini-aortic valve replacement" operation, on the other hand, is a risky procedure that should...

  10. Valve morphology effect in aortic coarctation flow using realistic silicon models and magnetic resonance imaging

    Science.gov (United States)

    Marrufo, Oscar; Solis-Najera, Sergio; Pibarot, Philippe; Kadem, Lyes; Kesharvarz-Motamed, Zahra; Rodriguez, Alfredo O.; Garcia, Julio

    2014-11-01

    Aortic valve morphology and phenotype may alter the aortic wall structure and its normal flow hemodynamics. However, the relationship between altered flow patterns and progression of wall pathology is often not fully understood in patients with aortic coartation and needs larger experimental work. In this study, we introduced a compatible experimental setup with magnetic resonance imaging (MRI) using a realistic aortic coarctation (AoCo) silicon model which can replicate physiological flow conditions (pressure, flow-wave, and systemic load). We evaluated the aortic valve hemodynamics of a normal tricuspid valve and a stenotic bicuspid valve using valve effective orifice area (EOA), peak and mean transvalvular pressure gradient (TPG). AoCo severity was assessed by the AoCo pressure gradient. For the tricuspid valve we obtained an EOA = 1.89 cm2, a peak TPG = 10 mmHg, and a mean TPG = 5 mmHg. For the bicuspid valve we obtained an EOA = 1.03 cm2, a peak TPG = 37 mmHg and a mean TPG = 13 mmHg. Furthermore, AoCo with tricuspid valve led to a peak AoCo pressure gradient (PG) = 11 mmHg and a mean PG = 5 mmHg. AoCo with bicuspid valve led to a peak PG = 6 mmHg and a mean PG = 3 mmHg. Aortic flow reattachment was more evident in presence of bicuspid valve and helical flow was present in all cases. This study showed that silicon prototyping in combination with MRI velocity measurements could successfully be used to assess hemodynamic effects of aortic valve morphology in aortic coarctation flow.

  11. Estudo comparativo da eficácia do etanol e do ácido L-glutâmico na prevenção da calcificação das cúspides e parede aórtica porcina: estudo experimental em ratos Comparative study on the efficacy of ethanol and of l-glutamic acid for preventing calcification of pig cusps and aortic wall: experimental study in rats

    Directory of Open Access Journals (Sweden)

    George Ronald Soncini da ROSA

    2002-06-01

    álcio/ mg tecido, E80% 30 dias (9,47 ± 2,59mg cálcio/mg tecido e E80% 60 dias (23,56±7,75 mg cálcio/mg tecido no grupo de AG 0,8% 15 dias (4,31±0,85 mg cálcio/mg tecido, AG 0,8% 30 dias (7,69±1,48 mg cálcio/mg tecido e AG 0,8% 60 dias (20,50± 1,22 mg cálcio/mg tecido com o grupo controle GDA 15 dias (7,34±1,32 mg cálcio/mg tecido, GDA 30 dias (9,28±0,76 mg cálcio/mg tecido e GDA 60 dias (27,60±1,08 mg cálcio/mg tecido. Na avaliação microscópica da cúspide aórtica houve uma progressiva calcificação naquelas submetidas à fixação com GDA. Este processo foi parcialmente encontrado com o AG 0,8% e totalmente ausente com o E80%. Quanto à avaliação referente aos segmentos da parede aórtica, também evidenciou-se progressiva calcificação, não sendo inibida pelos tratamentos com AG 0,8% e E80%. CONCLUSÕES: O pré-tratamento com etanol a 80% inibiu a calcificação nas cúspides aórticas porcinas, entretanto, não teve a mesma eficácia na parede aórtica. Contudo, o ácido L-glutâmico a 0,8% demonstrou minimizar a calcificação na parede aórtica. Estudos devem ser feitos para evidenciar se a ação anticalcificante do etanol a 80% mantém-se nas biopróteses aórticas porcinas se estas forem implantadas no sistema circulatório.INTRODUCTION: The glutataldehyde (GDA treated pigs cusps are one of most employed tissues in bioprosthesis, but is late post-implant calcification is main cause of its failure. BACKGROUND: This study aims at comparing and analyzing two methods (ethanol 80% and l-glutamic acid 0.8% to prevent calcification in pig cusps and aortic wall implanted subcutaneously in rats, the cusps and aortic wall segments of the control were in glutaraldehyde (GDA, during a 15, 30 and 60 days period after the implant. MATERIAL AND METHODS: We used 45 young rats, distributed in 3 groups of 15 rats each, which in turn were subdivided in 3 subgroups of 5 rats each, in which we implanted one cusp and one aortic wall segment in 2 subcutaneous

  12. 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

  13. Familial Abdominal Aortic Aneurysm : Clinical Features and Genetics

    NARCIS (Netherlands)

    K.M. van de Luijtgaarden (Koen)

    2016-01-01

    markdownabstractAbstract Cardiovascular disease is the most important cause of death in the world and encompasses occlusive as well as aneurysmal disease. The most common aneurysm in humans is the abdominal aortic aneurysm (AAA). The question is why the aorta dilates in aneurysmal disease and

  14. Familial Abdominal Aortic Aneurysm : Clinical Features and Genetics

    NARCIS (Netherlands)

    K.M. van de Luijtgaarden (Koen)

    2016-01-01

    markdownabstractAbstract Cardiovascular disease is the most important cause of death in the world and encompasses occlusive as well as aneurysmal disease. The most common aneurysm in humans is the abdominal aortic aneurysm (AAA). The question is why the aorta dilates in aneurysmal disease and occ

  15. Deformation of Congenital Bicuspid Aortic Valves in Systole

    Science.gov (United States)

    Szeto, Kai; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan

    2012-11-01

    Clinical studies have shown that patients with congenital bicuspid aortic valves (CBAVs) develop degenerative calcification of the leaflets at young ages compared to normal tricuspid aortic valves (TAVs). It has been hypothesized that the asymmetrical geometry of the leaflets in CBAVs and the associate changes in flow shear stresses and excessive strain rate levels are possible causes for the early calcification. Central to the validation of this hypothesis is the need to quantify the differences in strain rate levels between the BAVs and TAVs. We simulate the CBAVs by surgically stitching two of the leaflets of a porcine aortic valve together. To quantify strain differences, we performed in-vitro experiments in both BAVs and TAVs by tracking the 3-D motion of small dots marked on each leaflet surface. We then used phase-locked stereo photogrammetry to measure the strain rates in both radial and circumferential directions during the whole cardiac cycle. In the BAVs' case, the fused leaflet experiences an almost 30% increase in the radial stretching when fully open. RNA profiling of human aortic valve interstitial cells exposed to cyclic stretch shows that the increased stretch experienced by the BAVs results in increased levels of INTERLEUKINS (ILs) and other known inflammatory markers associated with aortic valve calcification. Together, these observations suggest that the abnormal stretch experienced by BAVs activates inflammation gene expression.

  16. Novel pharmacological strategies to prevent aortic complications in Marfan syndrome

    Institute of Scientific and Technical Information of China (English)

    Peter Matt; Friedrich Eckstein

    2011-01-01

    The Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the FBN1 gene.Recent molecular studies,most performed in mouse models,revealed that the MFS is more a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems.FBN1 haploinsufficiency and dysregulated transforming growth factor-beta (TGF-β)signaling seem to be critical for clinical manifestations in MFS including aortic root dilatation.Aortic root aneurysm and aortic dissection represent the main causes of morbidity and mortality in MFS.Most importantly,TGF-β antagonism through angiotensin Ⅱ type 1 receptor blockers (ARBs),for example losartan,has been shown to prevent and possibly reverse aortic root dilatation in a mouse model of MFS.A first human study on a small pediatric cohort confirmed those promising results in reducing the aortic root growth over a follow-up period of 12 to 47 months.So,a large multicenter trial has been set up and results should be available soon.Other therapeutic strategies which might be combined with losartan include traditional β-blockade,doxycyclin and statins.Such management could offer the first potential for primary prevention of clinical manifestations in MFS.

  17. To Estimate the Axial Elastic Modulus of Eye and Posterior Wall Thickness in Healthy Human Eye by Ultrasound Images and their Relation with Age and Gender

    Directory of Open Access Journals (Sweden)

    S. Shahbazi

    2007-06-01

    Full Text Available Introduction: Based on the invasive studies it has been shown that factors such as age, the progress of eye disorders, lens fibers compression and the biochemical changes of ocular matrix alter the physical characteristics and elastic properties of eye. In this study, a noninvasive method of estimating human eye elasticityis proposed and its relation with age and gender is evaluated using ultrasound images. Materials and Methods: To estimate eye elasticity, an especial loading system was designed and an external stress of 2614 ± 146 Pa which is less than the intraocular pressure of eye was applied to 20 eyes in an in vivo study. The pressure was measured using digital force gauge. The ultrasound images of B-mode were acquired prior to and post applying the stress. For the offline study throughout the loading process, the ultrasound images were saved as multi-frames into the computer by video grabber board. Monitoring, saving and further study of images were provided for the extraction of eye axial length and posterior wall thickness (PWT. The elasticity was estimated by measuring the relative changes of the axial length of eye, the posterior wall thickness and the applied stress. The statistical correlation of elastic modulus was analyzed based on age and gender. Results: The elastic modulus of the eye and the posterior wall thickness was estimated to be 51,777 ± 27304 and 14603 ± 4636 Pa, respectively. The obtained results indicated that there was no significant difference between the elastic parameters of the eye and the posterior wall thickness based on gender in both male and female group. The correlation analysis of the elastic parameter showed that there was significant difference between the eye and the posterior wall thickness based on age with a 95% confidence interval. Discussion and Conclusion: Based on the results obtained in this study the ultrasonic instruments might be used to estimate the hardness of eye lesions as well as eye

  18. Imaging of aortic valve dynamics in 4D OCT

    Directory of Open Access Journals (Sweden)

    Schnabel Christian

    2015-09-01

    Full Text Available The mechanical components of the heart, especially the valves and leaflets, are enormous stressed during lifetime. Therefore, those structures undergo different pathophysiological tissue transformations which affect cardiac output and in consequence living comfort of affected patients. These changes may lead to calcific aortic valve stenosis (AVS, the major heart valve disease in humans. The knowledge about changes of the dynamic behaviour during the course of this disease and the possibility of early stage diagnosis is of particular interest and could lead to the development of new treatment strategies and drug based options of prevention or therapy. 4D optical coherence tomography (OCT in combination with high-speed video microscopy were applied to characterize dynamic behaviour of the murine aortic valve and to characterize dynamic properties during artificial stimulation. We present a promising tool to investigate the aortic valve dynamics in an ex vivo disease model with a high spatial and temporal resolution using a multimodal imaging setup.

  19. [New aspects in aortic valve disease].

    Science.gov (United States)

    Tornos, P

    2001-01-01

    Renewed interest for aortic valve disease has evolved in recent years. Aortic valve replacement has become the second most frequent cause of cardiac surgery, following coronary bypass surgery. In addition, the etiologic and physiopathologic knowledge of this disorder has improved. In the present paper we analyze three aspects of the disease which are, at present, the subject of study and controversy: first, we discuss the possible relationship between degenerative aortic stenosis and atherosclerosis; second, the involvement of the aortic root in cases of bicuspid aortic valve; and third, the surgical indications in asymptomatic patients with either aortic stenosis or regurgitation.

  20. Chronic contained rupture of an abdominal aortic aneurysm presenting as a Grynfeltt lumbar hernia. A case report.

    Science.gov (United States)

    Dobbeleir, J; Fourneau, I; Maleux, G; Daenens, K; Vandekerkhof, J; Nevelsteen, A

    2007-06-01

    We report a unique case of chronic contained thoraco-abdominal aneurysm rupture presenting as a Grynfeltt lumbar hernia. A 79-year-old man presented with backpain and a bluish swelling in the left lumbar region in the presence of a non tender aortic aneurysm. CT scan confirmed contained rupture of a type IV thoraco-abdominal aortic aneurysm. The peri-aortic haematoma protruded through the lumbar wall causing a Grynfeltt lumbar hernia. The aneurysm was replaced through a thoraco-phreno-lumbotomy. The patient survived and is doing well six months postoperatively.

  1. Plasma cathepsin S and cystatin C levels and risk of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Lv, Bing-Jie; Lindholt, Jes Sanddal; Cheng, Xiang

    2012-01-01

    Human abdominal aortic aneurysm (AAA) lesions contain high levels of cathepsin S (CatS), but are deficient in its inhibitor, cystatin C. Whether plasma CatS and cystatin C levels are also altered in AAA patients remains unknown.......Human abdominal aortic aneurysm (AAA) lesions contain high levels of cathepsin S (CatS), but are deficient in its inhibitor, cystatin C. Whether plasma CatS and cystatin C levels are also altered in AAA patients remains unknown....

  2. [Paradigm shifts in aortic pathology: clinical and therapeutic implications. Clinical imaging in chronic and acute aortic syndromes. The aorta as a cause of cardiac disease].

    Science.gov (United States)

    Nistri, Stefano; Roghi, Alberto; Mele, Donato; Biagini, Elena; Chiodi, Elisabetta; Colombo, Ettore; d'Amati, Giulia; Leone, Ornella; Angelini, Annalisa; Basso, Cristina; Pepe, Guglielmina; Rapezzi, Claudio; Thiene, Gaetano

    2014-06-01

    Multimodal imaging plays a pivotal role in the assessment of the thoracic aorta, both in chronic and acute settings. Moving from improved knowledge on the structure and function of the aortic wall, as well as on its pathophysiology and histopathology, appropriate utilization of each imaging modality results into a better definition of the patient's need and proper treatment strategy. This review is aimed at highlighting the most critical aspects in this field, providing cardiologists with some novel clues for the imaging approach to patients with thoracic aortic disease.

  3. Intraventricular filling in physical models of the left ventricle: influence of aortic pressure

    Science.gov (United States)

    Nelsen, Nicholas; Samaee, Milad; Santhanakrishnan, Arvind

    2016-11-01

    Clinical studies using medical imaging have provided evidence on the formation of an intraventricular vortex in the left ventricle (LV) during diastolic phase of the cardiac cycle. However, the question of how the vortex characteristics are altered with aortic pressure remains unclear. This is of relevance to hypertensive heart disease and heart failure with normal ejection fraction. Using an experimental left heart simulator, we have previously shown that increasing LV wall stiffness results in reduction of the filling vortex circulation. In this study, we investigate the effects of varying aortic pressure in addition to wall stiffness. A series of flexible-walled LV models with varying wall stiffness were tested in a pulsatile flow loop. 2D particle image velocimetry was used to visualize intraventricular flow and calculate filling vortex circulation. The flow circuit was first setup with the least stiffness LV physical model, and tuned to physiological aortic pressure, cardiac output and ejection fraction. We then iteratively tested LV models with increasing stiffness without changing circuit variables. Comparisons of the filling vortex circulation with changing aortic pressure relative to the baseline and increased LV stiffness models will be presented.

  4. Therapeutic Prospect of Adipose-Derived Stromal Cells for the Treatment of Abdominal Aortic Aneurysm

    NARCIS (Netherlands)

    Parvizi, Mojtaba; Harmsen, Martin C.

    2015-01-01

    Aneurysm refers to the dilation of the vessel wall for more than 50%. Abdominal aortic aneurysm (AAA) refers to the dilation and weakening of all three layers of the abdominal aorta, which mostly occur infrarenally. The population aged above 50 years is at risk of AAA development, while a familiar

  5. Therapeutic Prospect of Adipose-Derived Stromal Cells for the Treatment of Abdominal Aortic Aneurysm

    NARCIS (Netherlands)

    Parvizi, Mojtaba; Harmsen, Martin C.

    2015-01-01

    Aneurysm refers to the dilation of the vessel wall for more than 50%. Abdominal aortic aneurysm (AAA) refers to the dilation and weakening of all three layers of the abdominal aorta, which mostly occur infrarenally. The population aged above 50 years is at risk of AAA development, while a familiar h

  6. Classification of gutter type in parallel stenting during endovascular aortic aneurysm repair

    NARCIS (Netherlands)

    Overeem, Simon P.; Boersen, Johannes T.; Schuurmann, Richte C L; Jebbink, Erik Groot; Slump, Cornelis H.; Reijnen, Michel M.P.J.; de Vries, Jean-Paul P.M.

    Objective: Gutters can be described as the loss of continuous apposition between the main body of the endograft, the chimney stent graft, and the aortic wall. Gutters have been associated with increased risk of type IA endoleaks and are considered to be the Achilles' heel of chimney endovascular

  7. Successful Anticoagulation Therapy for Antiphospholipid Syndrome with Mobile Aortic Thrombi

    Science.gov (United States)

    Park, Hyun Oh; Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Yang, Jun Ho; Lee, Chung-Eun; Kim, Jong-Duk

    2016-01-01

    Hypercoagulable states have been associated with aortic thrombosis. Antiphospholipid syndrome (APS) is one of the commonest types of acquired thrombophilia. We report the case of successful anticoagulation management in an APS patient with mobile thrombi within the aorta. A 58-year-old male patient presented to the emergency department (ED) with right-sided hemiparesis. His first symptoms were noted approximately 12–16 hours before presentation to the ED. Magnetic resonance imaging of the brain showed acute embolic infarction of the left frontal and parietotemporal lobes. Transesophageal echocardiography (TEE) and computed tomography angiography (CTA) demonstrated mobile thrombi attached to the wall of the ascending aorta and aortic arch. The patient was diagnosed with APS based on positivity of anti-beta-2 glycoprotein 1 antibodies, and was initiated on anticoagulation therapy. Repeated TEE and CTA revealed complete resolution of the thrombi after 12 days of treatment; the patient was discharged well. PMID:28042559

  8. The MAP kinase-activated protein kinase Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Li, Xichuan; Du, Wei; Zhao, Jingwen; Zhang, Lilin; Zhu, Zhiyan; Jiang, Linghuo

    2010-06-01

    Rck2p is the Hog1p-MAP kinase-activated protein kinase required for the attenuation of protein synthesis in response to an osmotic challenge in Saccharomyces cerevisiae. Rck2p also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. In this study, we demonstrate that the deletion of CaRCK2 renders C. albicans cells sensitive to, and CaRck2p translocates from the cytosol to the nucleus in response to, cell wall stresses caused by Congo red, Calcoflor White, elevated heat and zymolyase. However, the kinase activity of CaRck2p is not required for the cellular response to these cell wall stresses. Furthermore, transcripts of cell wall protein-encoding genes CaBGL2, CaHWP1 and CaXOG1 are reduced in C. albicans cells lacking CaRCK2. The deletion of CaRCK2 also reduces the in vitro filamentation of C. albicans and its virulence in a mouse model of systemic candidasis. The kinase activity of CaRck2p is required for the virulence, but not for the in vitro filamentation, in C. albicans. Therefore, Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen C. albicans.

  9. Percutaneous aortic valve replacement using a W-model valved stent: a preliminary feasibility study in sheep

    Institute of Scientific and Technical Information of China (English)

    BAI Yuan; ZONG Gang-jun; WANG Yan-yan; JIANG Hai-bin; LI Wei-ping; WU Hong; ZHAO Xian-xian; QIN Yong-wen

    2009-01-01

    Background Percutaneous aortic valve replacement is a promising strategy in the treatment of patients with aortic valve stenosis. And many kinds of valved stents have been implanted in selected patients worldwide. However, the clinical experience is still limited. We developed a W-model valved stent and evaluated the feasibility and safety of percutaneous implantation of the device in the native aortic valve position.Methods A self expanding nitinol stent with W-model, containing porcine pericardium valves in its proximal part, was implanted in six sheep by means of a 14 French catheter through the right common lilac artery under guidance of fluoroscopy. During stent deployment the original aortic valve was pushed against the aortic wall by the self expanding force of the stent while the new valve was expanded. These sheep were followed up shortly after procedure with supra-aortic angiogram and left ventriculography. Additionally, one sheep was sacrificed after the procedure for anatomic evaluation.Results It was possible to replace the aortic valve in the beating heart in four sheep. The procedure failed in two sheep due to coronary orifice occlusion in one case and severe aortic valve regurgitation in the other case. One sheep was killed one hour after percutaneous aortic valve replacement for anatomic evaluation. There were no signs of damage of the aortic intima, or of obstruction of the coronary orifice.Conclusions Percutaneous aortic valve replacement with a W-model valved stent in the beating heart is possible. Further studies are mandatory to assess safety and efficacy of this kind of valved stent in larger sample size and by longer follow-up period.

  10. Role of Microvascular Tone and Extracellular Matrix Contraction in the Regulation of Interstitial Fluid: Implications for Aortic Dissection.

    Science.gov (United States)

    Mallat, Ziad; Tedgui, Alain; Henrion, Daniel

    2016-09-01

    The pathophysiology of aortic dissection is poorly understood, and its risk is resistant to medical treatment. Most studies have focused on a proposed pathogenic role of transforming growth factor-β in Marfan disease and related thoracic aortic aneurysms and aortic dissections. However, clinical testing of this concept using angiotensin II type 1 receptor antagonists to block transforming growth factor-β signaling fell short of promise. Genetic mutations that predispose to thoracic aortic aneurysms and aortic dissections affect components of the extracellular matrix and proteins involved in cellular force generation. Thus, a role for dysfunctional mechanosensing in abnormal aortic wall remodeling is emerging. However, how abnormal mechanosensing leads to aortic dissection remains a mystery. Here, we review current knowledge about the regulation of interstitial fluid dynamics and myogenic tone and propose that alteration in contractile force reduces vascular tone in the microcirculation (here, aortic vasa vasorum) and leads to elevations of blood flow, transmural pressure, and fluid flux into the surrounding aortic media. Furthermore, reduced contractile force in medial smooth muscle cells coupled with alteration of structural components of the extracellular matrix limits extracellular matrix contraction, further promoting the formation of intramural edema, a critical step in the initiation of aortic dissection. The concept is supported by several pathophysiological and clinical observations. A direct implication of this concept is that drugs that lower blood pressure and limit interstitial fluid accumulation while preserving or increasing microvascular tone would limit the risk of dissection. In contrast, drugs that substantially lower microvascular tone would be ineffective or may accelerate the disease and precipitate aortic dissection.

  11. Gut Wall Metabolism. Application of Pre-Clinical Models for the Prediction of Human Drug Absorption and First-Pass Elimination.

    Science.gov (United States)

    Jones, Christopher R; Hatley, Oliver J D; Ungell, Anna-Lena; Hilgendorf, Constanze; Peters, Sheila Annie; Rostami-Hodjegan, Amin

    2016-05-01

    Quantifying the multiple processes which control and modulate the extent of oral bioavailability for drug candidates is critical to accurate projection of human pharmacokinetics (PK). Understanding how gut wall metabolism and hepatic elimination factor into first-pass clearance of drugs has improved enormously. Typically, the cytochrome P450s, uridine 5'-diphosphate-glucuronosyltransferases and sulfotransferases, are the main enzyme classes responsible for drug metabolism. Knowledge of the isoforms functionally expressed within organs of first-pass clearance, their anatomical topology (e.g. zonal distribution), protein homology and relative abundances and how these differ across species is important for building models of human metabolic extraction. The focus of this manuscript is to explore the parameters influencing bioavailability and to consider how well these are predicted in human from animal models or from in vitro to in vivo extrapolation. A unique retrospective analysis of three AstraZeneca molecules progressed to first in human PK studies is used to highlight the impact that species differences in gut wall metabolism can have on predicted human PK. Compared to the liver, pharmaceutical research has further to go in terms of adopting a common approach for characterisation and quantitative prediction of intestinal metabolism. A broad strategy is needed to integrate assessment of intestinal metabolism in the context of typical DMPK activities ongoing within drug discovery programmes up until candidate drug nomination.

  12. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

    DEFF Research Database (Denmark)

    Kloster, Brian O; Lund, Lars; Lindholt, Jes S

    2016-01-01

    to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. METHODS: The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten...... of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. RESULTS: All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned...... and histology. CONCLUSION: In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human...

  13. Spontaneous aortic dissection within an infrarenal AAA.

    Science.gov (United States)

    Griffin, Kathryn J; Bailey, Marc A; McAree, Barry; Mekako, Anthony; Berridge, David C; Nicholson, Tony; Scott, D Julian A

    2012-12-01

    Aortic dissection occurring in the infrarenal abdominal aorta is uncommon. We present the case of a patient presenting with an enlarging abdominal aortic aneurysm and concurrent dissection (with associated radiological imaging) and briefly discuss the literature relating to this phenomenon.

  14. Abdominal aortic aneurysm repair - open - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000240.htm Abdominal aortic aneurysm repair - open - discharge To use the sharing features ... References Orandi BJ, Black JH. Open repair of abdominal aortic aneurysms. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  15. Abdominal aortic feminism.

    Science.gov (United States)

    Mortimer, Alice Emily

    2014-11-14

    A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. 2014 BMJ Publishing Group Ltd.

  16. Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm.

    Science.gov (United States)

    Spear, Rafaelle; Boytard, Ludovic; Blervaque, Renaud; Chwastyniak, Maggy; Hot, David; Vanhoutte, Jonathan; Staels, Bart; Lemoine, Yves; Lamblin, Nicolas; Pruvot, François-René; Haulon, Stephan; Amouyel, Philippe; Pinet, Florence

    2015-05-18

    Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.

  17. Current aortic endografts for the treatment of abdominal aortic aneurysms.

    Science.gov (United States)

    Colvard, Benjamin; Georg, Yannick; Chakfe, Nabil; Swanstrom, Lee

    2016-05-01

    Endovascular Aneurysm Repair is a widely adopted method of treatment for patients with abdominal aortic aneurysms. The minimally invasive approach offered with EVAR has become popular not only among physicians and patients, but in the medical device industry as well. Over the past 25 years the global market for aortic endografts has increased rapidly, resulting in a wide range of devices from various companies. Currently, there are seven endografts approved by the FDA for the treatment of abdominal aortic aneurysms. These devices offer a wide range of designs intended to increase inclusion criteria while decreasing technical complications such as endoleak and migration. Despite advances in device design, secondary interventions and follow-up requirements remain a significant issue. New devices are currently being studied in the U.S. and abroad and may significantly reduce complications and secondary interventions.

  18. Management of bicuspid aortic valve with or without involvement of ascending aorta and aortic root.

    Science.gov (United States)

    Neragi-Miandoab, S

    2014-06-01

    Patients with a bicuspid aortic valve (BAV) constitute a heterogeneous population with variable clinical presentation and complications. More than 50% of the patients who require aortic valve replacement have a BAV, a condition that may be associated with dilation of ascending aorta and aortic insufficiency caused by cusp disease or aortic root pathology. Of the potential BAV-related complications, dilation of the aortic root and ascending aorta are among the most serious. The dilation of ascending aorta and aortic root have been the subject of controversy. Whereas some surgeons believe that the dilation of the aorta is caused by the hemodynamic properties of the BAV, others believe that the dilation of the aortic root is secondary to genetic defects associated with the BAV. Management of a BAV should be tailored to each patient's clinical condition. The surgical approach varies from aortic valve replacement to combined aortic valve and root replacement to aortic-valve-sparing root replacement.

  19. Open aortic surgery after thoracic endovascular aortic repair.

    Science.gov (United States)

    Coselli, Joseph S; Spiliotopoulos, Konstantinos; Preventza, Ourania; de la Cruz, Kim I; Amarasekara, Hiruni; Green, Susan Y

    2016-08-01

    In the last decade, thoracic endovascular aortic aneurysm repair (TEVAR) has emerged as an appealing alternative to the traditional open aortic aneurysm repair. This is largely due to generally improved early outcomes associated with TEVAR, including lower perioperative mortality and morbidity. However, it is relatively common for patients who undergo TEVAR to need a secondary intervention. In select circumstances, these secondary interventions are performed as an open procedure. Although it is difficult to assess the rate of open repairs after TEVAR, the rates in large series of TEVAR cases (>300) have ranged from 0.4 to 7.9 %. Major complications of TEVAR that typically necessitates open distal aortic repair (i.e., repair of the descending thoracic or thoracoabdominal aorta) include endoleak (especially type I), aortic fistula, endograft infection, device collapse or migration, and continued expansion of the aneurysm sac. Conversion to open repair of the distal aorta may be either elective (as for many endoleaks) or emergent (as for rupture, retrograde complicated dissection, malperfusion, and endograft infection). In addition, in select patients (e.g., those with a chronic aortic dissection), unrepaired sections of the aorta may progressively dilate, resulting in the need for multiple distal aortic repairs. Open repairs after TEVAR can be broadly classified as full extraction, partial extraction, or full salvage of the stent-graft. Although full and partial stent-graft extraction imply failure of TEVAR, such failure is generally absent in cases where the stent-graft can be fully salvaged. We review the literature regarding open repair after TEVAR and highlight operative strategies.

  20. Wonderful Walls

    Science.gov (United States)

    Greenman, Jim

    2006-01-01

    In this article, the author emphasizes the importance of "working" walls in children's programs. Children's programs need "working" walls (and ceilings and floors) which can be put to use for communication, display, storage, and activity space. The furnishings also work, or don't work, for the program in another sense: in aggregate, they serve as…

  1. Ambiguous walls

    DEFF Research Database (Denmark)

    Mody, Astrid

    2012-01-01

    The introduction of Light Emitting Diodes (LEDs) in the built environment has encouraged myriad applications, often embedded in surfaces as an integrated part of the architecture. Thus the wall as responsive luminous skin is becoming, if not common, at least familiar. Taking into account how wall...

  2. Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm.

    Science.gov (United States)

    Rubio-Navarro, Alfonso; Amaro Villalobos, Juan Manuel; Lindholt, Jes S; Buendía, Irene; Egido, Jesús; Blanco-Colio, Luis Miguel; Samaniego, Rafael; Meilhac, Olivier; Michel, Jean Baptiste; Martín-Ventura, José Luis; Moreno, Juan Antonio

    2015-12-15

    Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment and differentiation towards CD163 expressing macrophages ex vivo, in vitro and in human AAA. CD163 mRNA and protein expression was significantly higher in human AAA (n=7) vs. healthy wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich in hemosiderin and adjacent to neoangiogenic microvessels. Dual CD14/CD163 expression was observed in recently infiltrated monocytes surrounding microvessels. A higher release of soluble CD163 was observed in the conditioned medium from AAA (AAA-CM, n=10), mainly in the adventitial layer. Similar to Hb, AAA-CM induced CD163-dependent monocyte chemotaxis, especially on circulating monocytes from AAA patients. Hb or AAA-CM promoted differentiation towards CD163(high)/HLA-DR(low)-expressing macrophages, with enhanced Hb uptake, increased anti-inflammatory IL-10 secretion and decreased pro-inflammatory IL-12p40 release. All these effects were partially suppressed when Hb was removed from AAA-CM. Separate analysis on circulating monocytes reported increased percentage of pre-infiltrating CD14(++)CD16(+) monocytes in patients with AAA (n=21), as compared to controls (n=14). A significant increase in CD163 expression in CD14(++)CD16(+) monocyte subpopulation was observed in AAA patients. The presence of Hb in the adventitial AAA-wall promotes the migration and differentiation of activated circulating monocytes in AAA patients, explaining the existence of a protective CD163-macrophage phenotype that could take up the Hb present in the AAA-wall, avoiding its injurious effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Hemodynamics of the Aortic Jet and Implications for Detection of Aortic Stenosis Murmurs

    Science.gov (United States)

    Zhu, Chi; Seo, Junghee; Bakhshaee, Hani; Mittal, Rajat

    2016-11-01

    Cardiac auscultation with a stethoscope has served as the primary method for qualitative screening of cardiovascular conditions for over a hundred years. However, a lack of quantitative understanding of the flow mechanism(s) responsible for the generation of the murmurs, as well as the effect of intervening tissue on the propagation of these murmurs has been a significant limiting factor in the advancement of automated cardiac auscultation. In this study, a multiphysics computational modeling approach is used to investigate these issues. Direct numerical simulation (DNS) is used to explore the fluid dynamics of the jets formed at the aortic valve and the pressure fluctuations generated by the interaction of this jet with the aortic wall. Subsequently, structural wave propagation in the tissue is resolved by a high-order, linear viscoelastic wave solver in order to explore the propagation of the murmurs through a tissue-like material. The implications of these results for cardiac auscultation are discussed. The authors would like to acknowledge the financial support from NSF Grants IIS-1344772, CBET-1511200, and computational resource by XSEDE NSF Grant TG-CTS100002.

  4. Estudo micro-mesoscópico da parede lateral do seio cavernoso humano Human cavernous sinus: micro-mesoscopic study of the lateral wall

    Directory of Open Access Journals (Sweden)

    Renato Paulo Chopard

    1996-12-01

    Full Text Available Os autores estudam as estruturas contidas no seio cavernoso humano, tanto em seu interior como na sua parede lateral, através de cortes frontais seriados espessos. Mostram a importância desta parede que é freqüentemente usada como via de acesso cirúrgico às afecções presentes nesta estrutura venosa da dura-máterThe authors studied the structures of human cavernous sinus in its interior as well as on the lateral wall, utilizing thick, frontal, sequential sections. They show the significance of this wall, frequently used as surgical accessway to diseases encountered within this venous structure of the dura-mater.

  5. Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra

    Science.gov (United States)

    2016-03-09

    Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence

  6. Congenital bicuspid aortic valve in an English bulldog.

    Science.gov (United States)

    Visser, Lance C; Scansen, Brian A

    2013-03-01

    A bicuspid aortic valve (BAV) demonstrating moderate valvular stenosis and mild insufficiency was identified in an asymptomatic 1-year-old male cryptorchid English bulldog by transthoracic and transesophageal echocardiography. The BAV was most consistent with type 3 morphology, based upon human classification. Pulmonary valve dysplasia with mild pulmonary stenosis and a suspected persistent left cranial vena cava were also identified. Although BAV is the most common congenital cardiac malformation in humans, it is rare in the dog.

  7. Aortic root replacement with a pulmonary autograft

    NARCIS (Netherlands)

    R.B. Hokken (Raymond)

    1997-01-01

    textabstractAortic valve disease in the pediatric age group is usually a consequence of congenital aortic stenosis, which may be isolated or may be a part of an anomaly of the left ventricular outflow tract or the aortic root. Management of these patients is difficult. Neonates and infants with seve

  8. The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta

    Science.gov (United States)

    Ha, Hojin; Kim, Guk Bae; Kweon, Jihoon; Lee, Sang Joon; Kim, Young-Hak; Kim, Namkug; Yang, Dong Hyun

    2016-08-01

    Since the first observation of a helical flow pattern in aortic blood flow, the existence of helical blood flow has been found to be associated with various pathological conditions such as bicuspid aortic valve, aortic stenosis, and aortic dilatation. However, an understanding of the development of helical blood flow and its clinical implications are still lacking. In our present study, we hypothesized that the direction and angle of aortic inflow can influence helical flow patterns and related hemodynamic features in the thoracic aorta. Therefore, we investigated the hemodynamic features in the thoracic aorta and various aortic inflow angles using patient-specific vascular phantoms that were generated using a 3D printer and time-resolved, 3D, phase-contrast magnetic resonance imaging (PC-MRI). The results show that the rotational direction and strength of helical blood flow in the thoracic aorta largely vary according to the inflow direction of the aorta, and a higher helical velocity results in higher wall shear stress distributions. In addition, right-handed rotational flow conditions with higher rotational velocities imply a larger total kinetic energy than left-handed rotational flow conditions with lower rotational velocities.

  9. In vivo strain assessment of the abdominal aortic aneurysm.

    Science.gov (United States)

    Satriano, Alessandro; Rivolo, Simone; Martufi, Giampaolo; Finol, Ender A; Di Martino, Elena S

    2015-01-21

    The only criteria currently used to inform surgical decision for abdominal aortic aneurysms are maximum diameter (>5.5 cm) and rate of growth, even though several studies have identified the need for more specific indicators of risk. Patient-specific biomechanical variables likely to affect rupture risk would be a valuable addition to the science of understanding rupture risk and prove to be a life saving benefit for patients. Local deformability of the aorta is related to the local mechanical properties of the wall and may provide indication on the state of weakening of the wall tissue. We propose a 3D image-based approach to compute aortic wall strain maps in vivo. The method is applicable to a variety of imaging modalities that provide sequential images at different phases in the cardiac cycle. We applied the method to a series of abdominal aneurysms imaged using cine-MRI obtaining strain maps at different phases in the cardiac cycle. These maps could be used to evaluate the distensibility of an aneurysm at baseline and at different follow-up times and provide an additional index to clinicians to facilitate decisions on the best course of action for a specific patient.

  10. Attenuation of experimental aortic aneurysm formation in P-selectin knockout mice.

    Science.gov (United States)

    Hannawa, Kevin K; Cho, Brenda S; Sinha, Indranil; Roelofs, Karen J; Myers, Daniel D; Wakefield, Thomas J; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2006-11-01

    The aim of this study was to determine the role of P-selectin, an adhesion molecule found on the surface of activated platelets and endothelial cells during experimental aortic aneurysm formation. Infrarenal abdominal aortas of C57 black wild-type (WT) mice and P-selectin knockout (PKO) mice were measured in situ and then perfused with porcine pancreatic elastase (0.332 U/mL). Whole blood was drawn from the tail artery on day 2 pre-perfusion to determine total and differential white blood cell (WBC) counts. On day 14 postperfusion, aortic diameters (AD) of WT mice (N = 19) and PKO mice (N = 9) were measured. An aortic aneurysm was defined as a 100% or greater increase in AD from pre-perfusion measurement. Immunohistochemistry, including H&E, trichrome and von Gieson staining, was performed on harvested aortic tissue. Statistical analysis was performed by t-test and Fisher's exact test. There were no significant differences in peripheral leukocyte counts at baseline between the two groups. WT mice had significantly larger AD compared to PKO mice at day 14 postperfusion (116 % vs. 38 %, P < 0.001). Aortic aneurysm penetrance was 52% in WT mice, while 0% (P = 0.01) of PKO mice formed aneurysms. On histologic examination, WT mouse aortas were associated with a significant inflammatory response and degradation of elastin and collagen fibers, while PKO mouse aortas lacked signs of inflammation or vessel wall injury. P-selectin deficiency attenuates aneurysm formation in the elastase aortic perfusion model. This was associated with a blunting of the inflammatory response and preserved vessel wall intergrity following elastase perfusion in the P-selectin knockout mice. Further investigation to elucidate the independent contributions of endothelial cell and platelet P-selectin in experimental aortic aneurysm formation is required.

  11. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    Science.gov (United States)

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR.

  12. Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

    Science.gov (United States)

    Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

    2015-02-25

    Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  13. Arterial Stiffness Alterations and Inflammatory Response Following Endovascular Aortic Repair: Based on a Presentation at the 2013 VEITH Symposium, November 19-23, 2013 (New York, NY, USA).

    Science.gov (United States)

    Moulakakis, Konstantinos G; Mylonas, Spyridon N; Kakisis, John; Kadoglou, Nikolaos P E; Papadakis, Ioannis; Sfyroeras, George S; Antonopoulos, Constantine C N; Mantas, George; Ikonomidis, Ignatios; Liapis, Christos D

    2015-04-01

    Endovascular abdominal aortic aneurysm repair (EVAR) and thoracic aortic aneurysm repair (TEVAR) have been widely incorporated into clinical practice. However, changes in arterial stiffness and post-implantation syndrome after aortic endografting remain important issues under investigation. The aneurysm sac wall motion after successful EVAR and TEVAR reflects complex interactions between all the components of the excluded aneurysm, including true compliance of the aneurysm wall itself, intra-aneurysm sac pressure, remodeling of the thrombus, and mechanical characteristics of the endograft. Experimental and clinical studies have shown that aortic endografting results in increased arterial stiffness in animal models. It can be assumed that the alterations of aortic mechanical properties can have a direct impact on heart output. The long-term impact of these mechanical changes on cardiovascular outcomes and the potential effects of different endografts on hemodynamics are important issues under investigation. Post-implantation syndrome (PIS) is a systemic inflammatory response frequently observed after endovascular treatment of aortic pathologies. The main features of PIS include fever, leukocytosis, elevated C-reactive protein levels, and coagulation disturbances. Endograft design appears to influence this inflammatory response following aortic endografting; woven polyester endografts have been shown to be associated with greater inflammatory response compared to PTFE stent grafts. The purpose of this paper is to review the literature to elucidate arterial stiffness alterations and inflammatory response after EVAR and TEVAR and the impact of endograft design on aortic stiffness and the post-inflammatory response.

  14. Novel biaxial tensile test for studying aortic failure phenomena at a microscopic level.

    Science.gov (United States)

    Sugita, Shukei; Matsumoto, Takeo

    2013-01-11

    An aortic aneurysm is a local dilation of the aorta, which tends to expand and often results in a fatal rupture. Although larger aneurysms have a greater risk of rupture, some small aneurysms also rupture. Since the mechanism of aortic rupture is not well understood, clarification of the microstructure influencing the failure to rupture is important. Since aortic tissues are stretched biaxially in vivo, we developed a technique to microscopically observe the failure of an aortic rupture during biaxial stretch. A thinly sliced porcine thoracic aortic specimen was adhered to a circular frame and pushed onto a cylinder with a smaller diameter to stretch the specimen biaxially. To induce failure to rupture at the center, the specimen was thinned at the center of the hole as follows: the specimen was frozen while being compressed with metal plates having holes, which were 3 mm in diameter at their centers; the specimen was then sliced at 50-μm intervals and thawed. The ratio of the thickness at the center to the peripheral area was 99.5% for uncompressed specimens. The ratio decreased with an increase in the compression ratio εc and was 47.3% for specimens with εc = 40%. All specimens could be stretched until failure to rupture. The probability for crack initiation within the cylinder was 30%, respectively. Among specimens ruptured within the cylinder, 93% of those obtained from the mid-media showed crack initiation at the thin center area. Aortic tissues were successfully stretched biaxially until failure, and their crack initiation points were successfully observed under a microscope. This could be a very useful and powerful method for clarifying the mechanism of aortic rupture. We are planning to use this technique for a detailed investigation of events occurring at the point of failure when the crack initiates in the aortic aneurysm wall.

  15. Novel biaxial tensile test for studying aortic failure phenomena at a microscopic level

    Directory of Open Access Journals (Sweden)

    Sugita Shukei

    2013-01-01

    Full Text Available Abstract Background An aortic aneurysm is a local dilation of the aorta, which tends to expand and often results in a fatal rupture. Although larger aneurysms have a greater risk of rupture, some small aneurysms also rupture. Since the mechanism of aortic rupture is not well understood, clarification of the microstructure influencing the failure to rupture is important. Since aortic tissues are stretched biaxially in vivo, we developed a technique to microscopically observe the failure of an aortic rupture during biaxial stretch. Methods A thinly sliced porcine thoracic aortic specimen was adhered to a circular frame and pushed onto a cylinder with a smaller diameter to stretch the specimen biaxially. To induce failure to rupture at the center, the specimen was thinned at the center of the hole as follows: the specimen was frozen while being compressed with metal plates having holes, which were 3 mm in diameter at their centers; the specimen was then sliced at 50-μm intervals and thawed. Results The ratio of the thickness at the center to the peripheral area was 99.5% for uncompressed specimens. The ratio decreased with an increase in the compression ratio εc and was 47.3% for specimens with εc = 40%. All specimens could be stretched until failure to rupture. The probability for crack initiation within the cylinder was εc εc >30%, respectively. Among specimens ruptured within the cylinder, 93% of those obtained from the mid-media showed crack initiation at the thin center area. Conclusions Aortic tissues were successfully stretched biaxially until failure, and their crack initiation points were successfully observed under a microscope. This could be a very useful and powerful method for clarifying the mechanism of aortic rupture. We are planning to use this technique for a detailed investigation of events occurring at the point of failure when the crack initiates in the aortic aneurysm wall.

  16. Infectious or Noninfectious? Ruptured, Thrombosed Inflammatory Aortic Aneurysm with Spondylolysis

    Energy Technology Data Exchange (ETDEWEB)

    Stefanczyk, Ludomir; Elgalal, Marcin, E-mail: telgalal@yahoo.co.uk [Medical University of Lodz, Department of Radiology and Diagnostic Imaging (Poland); Papiewski, Andrzej [Medical University of Lodz, Department of Gastroenterological Surgery (Poland); Szubert, Wojciech [Medical University of Lodz, Department of Radiology and Diagnostic Imaging (Poland); Szopinski, Piotr [Institute of Hematology and Transfusion Medicine, Clinic of Vascular Surgery (Poland)

    2013-06-15

    Osteolysis of vertebrae due to inflammatory aortic aneurysm is rarely observed. However, it is estimated that up to 10 % of infectious aneurysms coexist with bone tissue destruction, most commonly the vertebrae. Inflammatory aneurysms with no identified infection factor, along with infiltration of adjacent muscle and in particular extensive destruction of bone tissue have rarely been described in the literature. A case of inflammatory aneurysm with posterior wall rupture and inflammatory infiltration of the iliopsoas muscle and spine, together with extensive vertebral body destruction, is presented. The aneurysm was successfully treated with endovascular aneurysm repair EVAR.

  17. Double prosthetic aortic valve. Case report.

    Science.gov (United States)

    Liddicoat, J E; Bekassy, S M; De Bakey, M E

    1975-05-01

    A 55-year-old man underwent insection of a Hufnagel valve into his descending thoracic aorta for aortic valve insufficiency 18 years ago. He remained asymptomatic for 16 years. Because of progressive left ventricular failure his incompetent aortic valve was replaced with a De Bakey carbon ball aortic valve prosthesis 2 years later. Currently, 21 months after the operation, he is doing well with two aortic valves. Review of the literature suggests that he is the first patient reported with two aortic valves functioning concomitantly and one of the longest surviving patients with a Hufnagel valve.

  18. Obtaining the biomechanical behavior of ascending aortic aneurysm via the use of novel speckle tracking echocardiography.

    Science.gov (United States)

    Alreshidan, Mohammed; Shahmansouri, Nastaran; Chung, Jennifer; Lash, Vynka; Emmott, Alexander; Leask, Richard L; Lachapelle, Kevin

    2017-04-01

    Ex vivo measurement of ascending aortic biomechanical properties may help understand the risk for rupture or dissection of dilated ascending aortas. A validated in vivo method that can predict aortic biomechanics does not exist. Speckle tracking transesophageal echocardiography (TEE) has been used to measure ventricular stiffness; we sought to determine whether speckle TEE could be adapted to estimate aortic stiffness in vivo and compare these findings with those obtained by ex vivo tissue measurements. A total of 17 patients undergoing ascending aortic resection were recruited to with a mean aortic diameter was 56.16 ± 15 mm. Intraoperative speckle TEE tracking analysis was used to calculate aortic stiffness index using the following equation: β2=ln(SBP/DBP)/AoS, where β2 is the stiffness index; SBP is systolic blood pressure; DBP is diastolic blood pressure; and AoS is the circumferential strain. Ex vivo stiffness was obtained by mechanical tissue testing according to previously described methods. The aortic ring at the pulmonary trunk was divided into 4 equal quadrants. The in vivo stiffness index for the inner curvature, anterior wall, outer curvature, and posterior wall were 0.0544 ± 0.0490, 0.0295 ± 0.0199, 0.0411 ± 0.0328, and 0.0502 ± 0.0320, respectively. The mean ex vivo 25% apparent stiffness for inner curvature, anterior wall, outer curvature, and posterior wall were 0.0616 ± 0.0758 MPa, 0.0352 ± 0.00992 MPa, 0.0405 ± 0.0199 MPa, and 0.0327 ± 0.0106 MPa, respectively. The patient-matched ex vivo 25% apparent stiffness and in vivo stiffness index were not significantly different (P = .8617, 2-way analysis of variance with repeated measures). The use of speckle TEE appears to be a promising technique to estimate ex vivo mechanical properties of the ascending aortic tissue. Copyright © 2016 The American Association for Thoracic Surgery. All rights reserved.

  19. MHHT-Based Method for Analysis of Micro-Doppler Signatures for Human Finer-Grained Activity Using Through-Wall SFCW Radar

    Directory of Open Access Journals (Sweden)

    Fugui Qi

    2017-03-01

    Full Text Available Ultra-wideband radar-based penetrating detection and recognition of human activities has become a focus on remote sensing in various military applications in recent years, such as urban warfare, hostage rescue, and earthquake post-disaster rescue. However, an excellent micro-Doppler signature (MDS extracting method of human motion with high time-frequency resolution, outstanding anti-interference ability, and extensive adaptability, which aims to provide favorable and more detailed features for human activity recognition and classification, especially in the non-free space detection environment, is in great urgency. To cope with the issue, a multiple Hilbert-Huang transform (MHHT method is proposed for high-resolution time-frequency analysis of finer-grained human activity MDS hidden in ultra-wideband (UWB radar echoes during the through-wall detection environment. Based on the improved HHT with effective intrinsic mode function (IMF selection according to the cosine similarity (CS principle, the improved HHT is applied to each channel signal in the effective channel scope of the UWB radar signal and then integrated along the range direction. The activities of swinging one or two arms while standing at a spot 3 m from a wall were used to validate the abilities of the proposed method for extracting and separating the MDS of different moving body structures with a high time-frequency resolution. Simultaneously, the corresponding relationship between the frequency components in MHHT-based spectra and structures of the moving human body was demonstrated according to the radar Doppler principle combined with the principle of human body kinematics. Moreover, six common finer-grained human activities and a piaffe at different ranges under the through-wall detection environment were exploited to confirm the adaptability of the novel method for different activities and pre-eminent anti-interference ability under a low signal-noise-clutter ratio (SNCR

  20. A negative correlation between human carotid atherosclerotic plaque progression and plaque wall stress: in vivo MRI-based 2D/3D FSI models.

    Science.gov (United States)

    Tang, Dalin; Yang, Chun; Mondal, Sayan; Liu, Fei; Canton, Gador; Hatsukami, Thomas S; Yuan, Chun

    2008-01-01

    It is well accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses (FSS). However, this mechanism cannot explain why advanced plaques continue to grow under elevated FSS conditions. In vivo magnetic resonance imaging (MRI)-based 2D/3D multi-component models with fluid-structure interactions (FSI, 3D only) for human carotid atherosclerotic plaques were introduced to quantify correlations between plaque progression measured by wall thickness increase (WTI) and plaque wall (structure) stress (PWS) conditions. A histologically validated multi-contrast MRI protocol was used to acquire multi-year in vivo MRI images. Our results using 2D models (200-700 data points/patient) indicated that 18 out of 21 patients studied showed significant negative correlation between WTI and PWS at time 2 (T2). The 95% confidence interval for the Pearson correlation coefficient is (-0.443,-0.246), p<0.0001. Our 3D FSI model supported the 2D correlation results and further indicated that combining both plaque structure stress and flow shear stress gave better approximation results (PWS, T2: R(2)=0.279; FSS, T1: R(2)=0.276; combining both: R(2)=0.637). These pilot studies suggest that both lower PWS and lower FSS may contribute to continued plaque progression and should be taken into consideration in future investigations of diseases related to atherosclerosis.

  1. Wall Turbulence.

    Science.gov (United States)

    Hanratty, Thomas J.

    1980-01-01

    This paper gives an account of research on the structure of turbulence close to a solid boundary. Included is a method to study the flow close to the wall of a pipe without interferring with it. (Author/JN)

  2. Transfemoral transcatheter aortic valve implantation in a patient with a severe aortic stenosis and cardiogenic shock requiring intra-aortic balloon pump support.

    Science.gov (United States)

    Chodór, Piotr; Wilczek, Krzysztof; Przybylski, Roman; Świątkowski, Andrzej; Głowacki, Jan; Kalarus, Zbigniew; Zembala, Marian

    2015-01-01

    The following paper presents a patient with severe aortic stenosis and severely reduced left ventricular ejection fraction with intra-aortic balloon pump counterpulsation support, who underwent transfemoral aortic valve implantation of a CoreValve prosthesis.

  3. Transfemoral transcatheter aortic valve implantation in a patient with a severe aortic stenosis and cardiogenic shock requiring intra-aortic balloon pump support

    OpenAIRE

    Chodór, Piotr; Wilczek, Krzysztof; Przybylski, Roman; Świątkowski, Andrzej; Głowacki, Jan; Kalarus, Zbigniew; Zembala, Marian

    2015-01-01

    The following paper presents a patient with severe aortic stenosis and severely reduced left ventricular ejection fraction with intra-aortic balloon pump counterpulsation support, who underwent transfemoral aortic valve implantation of a CoreValve prosthesis.

  4. Recombinant human bone morphogenetic protein 2-induced heterotopic ossification of the retroperitoneum, psoas muscle, pelvis and abdominal wall following lumbar spinal fusion

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Raj K. [The George Washington University School of Medicine, Washington, DC (United States); Moncayo, Valeria M.; Pierre-Jerome, Claude; Terk, Michael R. [Emory University School of Medicine, Radiology Department, Musculoskeletal Division, Atlanta, GA (United States); Smitson, Robert D. [Emory University School of Medicine, Atlanta, GA (United States)

    2010-05-15

    A 45-year-old man presented with vertebral collapse at L5 as an initial manifestation of multiple myeloma and underwent spinal fusion surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2). Subsequent computed tomography (CT) scans and X-rays revealed heterotopic ossification of the left psoas muscle, pelvis, and anterior abdominal wall. While the occurrence of heterotopic ossification has previously been reported when rhBMP-2 has been used for spinal fusion surgery, this case demonstrates that it can occur to a much greater degree than previously seen. (orig.)

  5. Aortic Root Enlargement or Sutureless Valve Implantation?

    Directory of Open Access Journals (Sweden)

    Nikolaos G. Baikoussis

    2016-11-01

    Full Text Available Aortic valve replacement (AVR in patients with a small aortic annulus is a challenging issue. The importance of prosthesis–patient mismatch (PPM post aortic valve replacement (AVR is controversial but has to be avoided. Many studies support the fact that PPM has a negative impact on short and long term survival. In order to avoid PPM, aortic root enlargement may be performed. Alternatively and keeping in mind that often some comorbidities are present in old patients with small aortic root, the Perceval S suturelles valve implantation could be a perfect solution. The Perceval sutureless bioprosthesis provides reasonable hemodynamic performance avoiding the PPM and providing the maximum of aortic orifice area. We would like to see in the near future the role of the aortic root enlargement techniques in the era of surgical implantation of the sutureless valve (SAVR and the transcatheter valve implantation (TAVI.

  6. Remodelling of the aortic root in severe tricuspid aortic stenosis: implications for transcatheter aortic valve implantation

    Energy Technology Data Exchange (ETDEWEB)

    Stolzmann, Paul; Desbiolles, Lotus; Scheffel, Hans; Leschka, Sebastian; Marincek, Borut; Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic Radiology, Zurich (Switzerland); Knight, Joseph; Kurtcuoglu, Vartan; Poulikakos, Dimos [Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich (Switzerland); Maier, Willibald [University Hospital Zurich, Cardiovascular Center, Zurich (Switzerland); Plass, Andre [University Hospital Zurich, Clinic for Cardiovascular Surgery, Zurich (Switzerland)

    2009-06-15

    Detailed knowledge of aortic root geometry is a prerequisite to anticipate complications of transcatheter aortic valve (TAV) implantation. We determined coronary ostial locations and aortic root dimensions in patients with aortic stenosis (AS) and compared these values with normal subjects using computed tomography (CT). One hundred consecutive patients with severe tricuspid AS and 100 consecutive patients without valvular pathology (referred to as the controls) undergoing cardiac dual-source CT were included. Distances from the aortic annulus (AA) to the left coronary ostium (LCO), right coronary ostium (RCO), the height of the left coronary sinus (HLS), right coronary sinus (HRS), and aortic root dimensions [diameters of AA, sinus of Valsalva (SV), and sino-tubular junction(STJ)] were measured. LCO and RCO were 14.9 {+-} 3.2 mm (8.2-25.9) and 16.8 {+-} 3.6 mm (12.0-25.7) in the controls, 15.5 {+-} 2.9 mm (8.8-24.3) and 17.3 {+-} 3.6 mm (7.3-26.0) in patients with AS. Controls and patients with AS had similar values for LCO (P = 0.18), RCO (P = 0.33) and HLS (P = 0.88), whereas HRS (P < 0.05) was significantly larger in patients with AS. AA (r = 0.55,P < 0.001), SV (r = 0.54,P < 0.001), and STJ (r = 0.52,P < 0.001) significantly correlated with the body surface area in the controls; whereas no correlation was found in patients with AS. Patients with AS had significantly larger AA (P < 0.01) and STJ (P < 0.01) diameters when compared with the controls. In patients with severe tricuspid AS, coronary ostial locations were similar to the controls, but a transverse remodelling of the aortic root was recognized. Owing to the large distribution of ostial locations and the dilatation of the aortic root, CT is recommended before TAV implantation in each patient. (orig.)

  7. Characterizing the role of cell-wall β-1,3-exoglucanase Xog1p in Candida albicans adhesion by the human antimicrobial peptide LL-37.

    Directory of Open Access Journals (Sweden)

    Pei-Wen Tsai

    Full Text Available Candida albicans is the major fungal pathogen of humans. Its adhesion to host-cell surfaces is the first critical step during mucosal infection. Antimicrobial peptides play important roles in the first line of mucosal immunity against C. albicans infection. LL-37 is the only member of the human cathelicidin antimicrobial peptide family and is commonly expressed in various tissues, including epithelium. We previously showed that LL-37 significantly reduced C. albicans adhesion to plastic, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. The inhibitory effect of LL-37 on cell adhesion occurred via the binding of LL-37 to cell-wall carbohydrates. Here we showed that formation of LL-37-cell-wall protein complexes potentially inhibits C. albicans adhesion to polystyrene. Using phage display and ELISA, we identified 10 peptide sequences that could bind LL-37. A BLAST search revealed that four sequences in the major C. albicans cell-wall β-1,3-exoglucanase, Xog1p, were highly similar to the consensus sequence derived from the 10 biopanned peptides. One Xog1p-derived peptide, Xog1p(90-115, and recombinant Xog1p associated with LL-37, thereby reversing the inhibitory effect of LL-37 on C. albicans adhesion. LL-37 reduced Xog1p activity and thus interrupted cell-wall remodeling. Moreover, deletion of XOG1 or another β-1,3-exoglucanase-encoding gene EXG2 showed that only when XOG1 was deleted did cellular exoglucanase activity, cell adhesion and LL-37 binding decrease. Antibodies against Xog1p also decreased cell adhesion. These data reveal that Xog1p, originally identified from LL-37 binding, has a role in C. albicans adhesion to polystyrene and, by inference, attach to host cells via direct or indirect manners. Compounds that target Xog1p might find use as drugs that prevent C. albicans infection. Additionally, LL-37 could potentially be used to screen for other cell-wall components involved in fungal cell adhesion.

  8. AORTIC ANEURYSM: A RARE CAUSE OF ORTNER’S SYNDROME

    Directory of Open Access Journals (Sweden)

    Sukanta

    2014-11-01

    Full Text Available A 60 year old male patient presented with hoarseness of voice lasting for 2 months. First he was examined by the otorhinolaryngologist of our hospital, who noticed absence of movements of the left vocal cord. Chest X-ray showed a large opacity in the left upper zone and the patient was referred to the pulmonologist. His general physical examination was unremarkable not having any stigmata of Marfan's or Ehler Danlos syndrome. On chest auscultation, a systolic flow murmur was audible and there was decreased breath sound in the left infraclavicular area. Bronchoscopy revealed absence of movement of left vocal cord. His trans-thoracic echocardiography revealed degenerative aortic and mitral valve disease with mild aortic regurgitation and mild mitral regurgitation with dilated aortic aneurysm. A contrast enhanced CT scan of thorax and CT Angio Aortogram revealed fusiform aneurysmal dilatation of the arch of aorta with diameter of 6.2 cm over a length of 12.3 cm showing intraluminal partial thrombus with wall calcification. The patient was advised to undergo surgery. However, after detailed discussion with him and his family, they decided for medical management in view of his advanced age

  9. Deformation Differences between Tricuspid and Bicuspid Aortic Valves in Vitro

    Science.gov (United States)

    Szeto, Kai; Rodriguez-Rodriguez, Javier; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan C.

    2011-11-01

    It has been shown in clinical studies that patients with congenital bicuspid aortic valves (CBAVs) develop degenerative calcification of the leaflets at young ages compared to patients with the normal tricuspid aortic valves (TAVs). It has been hypothesized that the asymmetrical geometry of the leaflets in CBAVs, flow shear stresses (SS), disturbed flow, and excessive strain rate levels are possible causes for the early calcification and stenosis. Central to the validation of this hypothesis is the need to quantify the differences in strain rate levels between the BAVs and TAVs. We simulate the CBAVs by surgically stitching two of the leaflets of a porcine aortic valve together. To quantify strain differences, we performed in-vitro experiments in both trileaflet and bileaflet valves by tracking the motion of small ink dots marked on each leaflet surface. We then used phase-locked stereo photogrammetry to reconstruct at each instant of time the 3D surface of the leaflets and measure the strain rates in both radial and circumferential directions during the whole cardiac cycle. Our results indicate that the total strain rate of the simulated BAVs is about 15 to 20% higher than the normal leaflets of TAVs at systole. In the BAVs' case, the fused leaflet stretches radially up to 25% higher than the reference length. The excessive stretching in both directions in the fused leaflet results in large changes in the flow patterns and associated wall SS.

  10. Abdominal aortic aneurysm and histological, clinical, radiological correlation.

    Science.gov (United States)

    Rodella, Luigi Fabrizio; Rezzani, Rita; Bonomini, Francesca; Peroni, Michele; Cocchi, Marco Angelo; Hirtler, Lena; Bonardelli, Stefano

    2016-04-01

    To date, the pathogenesis of abdominal aortic aneurism (AAA) still remains unclear. As such, the aim of this study was to evaluate changes of the aortic structure during AAA. We analysed the microscopic frame of vessels sections, starting from the primum movens leading to abnormal dilatation. AAA samples were collected and processed through various staining methods (Verhoeff-Van Gieson, Masson Goldner, Sirius Red). Subsequently, the vessel morphology and collagenic web of the tunica media and adventitia were determined and the amount of type I and type III collagen was measured. We also applied immune-histochemistry markers for CD34 and PGP 9.5 in order to identify vascular and nerve structures in the aorta. Immune-positivity quantification was used to calculate the percentage of the stained area. We found increasing deposition of type I collagen and reduced type III collagen in both tunica media and adventitia of AAA. The total amount of vasa vasorum, marked with CD34, and nerva vasorum, marked with PGP 9.5, was also higher in AAA samples. Cardiovascular risk factors (blood pressure, dyslipidemia, cigarette smoking) and radiological data (maximum aneurism diameter, intra-luminal thrombus, aortic wall calcification) increased these changes. These results suggest that the tunica adventitia may have a central role in the pathogenesis of AAA as clearly there are major changes characterized by rooted inflammatory infiltration. The presence of immune components could explain these modifications within the framework of the aorta.

  11. Spectrum of Aortic Valve Abnormalities Associated with Aortic Dilation Across Age Groups in Turner Syndrome

    Science.gov (United States)

    Olivieri, Laura J.; Baba, Ridhwan Y.; Arai, Andrew E.; Bandettini, W. Patricia; Rosing, Douglas R.; Bakalov, Vladimir; Sachdev, Vandana; Bondy, Carolyn A.

    2014-01-01

    Background Congenital aortic valve fusion is associated with aortic dilation, aneurysm and rupture in girls and women with Turner syndrome (TS). Our objective was to characterize aortic valve structure in subjects with TS, and determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. Methods and Results The aortic valve and thoracic aorta were characterized by cardiovascular magnetic resonance imaging in 208 subjects with TS in an IRB-approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve, and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve (TAV) 64%(n=133), partially fused aortic valve (PF) 12%(n=25), bicuspid aortic valve (BAV) 23%(n=47), and unicuspid aortic valve (UAV) 1%(n=3). Age and body surface area (BSA) were similar in the 4 valve morphology groups. There was a significant trend, independent of age, towards larger BSA-indexed ascending aortic diameters (AADi) with increasing valve fusion. AADi were (mean +/− SD) 16.9 +/− 3.3 mm/m2, 18.3 +/− 3.3 mm/m2, and 19.8 +/− 3.9 mm/m2 (p<0.0001) for TAV, PF and BAV+UAV respectively. PF, BAV, and UAV were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve. Conclusions Aortic valve abnormalities in TS occur with a spectrum of severity, and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased AADi. PMID:24084490

  12. Retrograde coronary sinus versus aortic root perfusion with cold cardioplegia: randomized study of levels of cardiac enzymes in 40 patients

    Energy Technology Data Exchange (ETDEWEB)

    Guiraudon, G.M.; Campbell, C.S.; McLellan, D.G.; Kostuk, W.J.; Purves, P.D.; MacDonald, J.L.; Cleland, A.G.; Tadros, N.B.

    1986-11-01

    Myocardial injury was assessed with the use of enzyme indexes in 40 patients randomly assigned to one of two groups undergoing coronary artery bypass surgery. Twenty patients received cold cardioplegia delivered by retrograde coronary sinus perfusion and 20 received cardioplegic solution by anterograde aortic root perfusion. Creatine kinase isoenzyme MB and lactate dehydrogenese isoenzyme 1 and isoenzyme 2 assays were carried out on blood samples obtained from the coronary sinus before aortic cross-clamping and 0, 5, and 30 min after aortic unclamping. Levels of these enzymes were also obtained from venous blood samples before aortic cross-clamping and 3, 8, 14, and 20 hr after aortic unclamping and 2, 3, 4, and 5 days after surgery. Preoperative and postoperative hemodynamic measurements (Swan-Ganz catheter) and radionuclide wall motion studies were also obtained for comparison. There was no overall significant difference between the two groups postoperatively in terms of enzyme indexes, hemodynamic measurements, or results of wall motion studies. We conclude that retrograde coronary sinus perfusion is an alternative to aortic root perfusion in delivering cold cardioplegia. More studies are required to determine which subgroup of patients with coronary artery disease may benefit from retrograde coronary perfusion.

  13. Myocardial oxygen supply/demand ratio in aortic stenosis: hemodynamic and echocardiographic evaluation of patients with and without angina pectoris.

    Science.gov (United States)

    Nadell, R; DePace, N L; Ren, J F; Hakki, A H; Iskandrian, A S; Morganroth, J

    1983-08-01

    Angina pectoris is a common symptom in patients with aortic stenosis without coronary artery disease. To investigate the correlates of angina pectoris, echocardiographic and hemodynamic data from 44 patients with aortic stenosis and no coronary artery disease (mean age 56 +/- 10 years) were analyzed. Twenty-three patients had no angina pectoris and 21 patients had angina pectoris. The ratio of the diastolic pressure-time index (area between the aortic and left ventricular pressure curves during diastole) to the systolic pressure-time index (area under the left ventricular pressure curve during systole), an index of the oxygen supply/demand ratio, was not different in patients with or without angina pectoris. There were no differences between patients with and without angina pectoris in echocardiographically determined wall thickness, chamber size, systolic and diastolic wall stress and left ventricular mass; in electrocardiographically defined voltage; and in hemodynamically defined aortic valve area, transaortic gradient and stroke work index. Thus, echocardiographic and hemodynamic measurements at rest are not significantly different in the presence or absence of angina pectoris in patients with aortic stenosis. Dynamic data appear to be essential for evaluation of the mechanisms of angina pectoris in patients with aortic stenosis.

  14. The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice

    DEFF Research Database (Denmark)

    Wintmo, P.; Johansen, Søren Høyer; Hansen, P. B L

    2017-01-01

    aneurysms. Apolipoprotein E (ApoE) knockout (-/-) and AQP1-/-ApoE-/- mice were developed and fed Western diet (WD) for 8 and 16 weeks to accelerate the atherosclerosis process. In ApoE-/- and AQP1-/-ApoE-/- mice abdominal aortic aneurysms (AAA) were induced by angiotensin II (ANGII) infusion by osmotic...... minipumps for 4 weeks. Results: In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n = 7-9, P ... aortic aneurysmal wall, AQP1 immunoreactivity was associated with microvascular structures. The atherosclerotic lesion burden was enhanced significantly in ANGII-infused AQP1-/-ApoE-/- mice compared with ApoE-/- mice, but neither incidence nor progression of AAA was different. The aortic lesion burden...

  15. 9p21.3 Coronary Artery Disease Risk Variants Disrupt TEAD Transcription Factor-Dependent Transforming Growth Factor β Regulation of p16 Expression in Human Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Almontashiri, Naif A M; Antoine, Darlène; Zhou, Xun; Vilmundarson, Ragnar O; Zhang, Sean X; Hao, Kennedy N; Chen, Hsiao-Huei; Stewart, Alexandre F R

    2015-11-24

    The mechanism whereby the 9p21.3 locus confers risk for coronary artery disease remains incompletely understood. Risk alleles are associated with reduced expression of the cell cycle suppressor genes CDKN2A (p16 and p14) and CDKN2B (p15) and increased vascular smooth muscle cell proliferation. We asked whether risk alleles disrupt transcription factor binding to account for this effect. A bioinformatic screen was used to predict which of 59 single nucleotide polymorphisms at the 9p21.3 locus disrupt (or create) transcription factor binding sites. Electrophoretic mobility shift and luciferase reporter assays examined the binding and functionality of the predicted regulatory sequences. Primary human aortic smooth muscle cells (HAoSMCs) were genotyped for 9p21.3, and HAoSMCs homozygous for the risk allele showed reduced p15 and p16 levels and increased proliferation. rs10811656 and rs4977757 disrupted functional TEF-1 TEC1 AbaA domain (TEAD) transcription factor binding sites. TEAD3 and TEAD4 overexpression induced p16 in HAoSMCs homozygous for the nonrisk allele, but not for the risk allele. Transforming growth factor β, known to activate p16 and also to interact with TEAD factors, failed to induce p16 or to inhibit proliferation of HAoSMCs homozygous for the risk allele. Knockdown of TEAD3 blocked transforming growth factor β-induced p16 mRNA and protein expre