Arterial Wall Response to ex vivo Exposure to Oscillatory Shear Stress

Abstract

Background: The aim of this study was to analyze the arterial wall response to plaque-prone hemodynamic environments, known to occur mainly in areas of arterial trees such as bifurcations and branching points. In these areas, the vasculature is exposed to cyclically reversing flow that induces an endothelial dysfunction predisposing thus arteries to local development of atherosclerotic plaques. Methods: We used an ex vivo perfusion system that allows culturing arterial segments under different hemodynamic conditions. Porcine carotid arteries were exposed for 3 days to unidirectional high and low shear stress (6 ± 3 and 0.3 ± 0.1 dyn/cm²) as well as to oscillatory shear stress (0.3 ± 3 dyn/cm²). This latter condition mimics the hemodynamics present at plaque-prone areas. At the end of the perfusion, the influence of different flow patterns on arterial metabolism was assessed in terms of matrix turnover as well as of smooth muscle cell function, differentiation and migration. Results: Our results show that after 3 days of perfusion none of the applied conditions influence smooth muscle cell phenotype retaining their full contraction capacity. However, an increase in the expression level of matrix metalloproteinase-2 and -9, as well as a decrease in plasminogen activator inhibitor-1 expression were observed in arteries exposed to oscillatory shear stress when compared to arteries exposed to unidirectional shear stress. Conclusion: These observations suggest that plaque-prone hemodynamic environment triggers a vascular wall remodelling process and promotes changes in arterial wall metabolism, with important implication in atherogenesis.

Effects of Reduced Cyclic Stretch on Vascular Smooth Muscle Cell Function of Pig Carotids Perfused Ex Vivo

“…Details on ex vivo arterial support system have been given earlier. 14 The arterial segments were perfused for 24 h with M199-EBS (Amersham) containing 5% fetal calf serum. The medium was constantly gas-infused with 5% CO 2 and 95% air.…”

“…Protein expression and gelatinolytic activity were assessed using immunoblot and zymography techniques, respectively, as described earlier. 14 Protein was extracted from the samples with a Brij-35 lyses buffer (50 mmol/l Tris pH 7.5, 1 mol/l NaCl, 2 mol/l Urea, 0.1% Brij-35, and 1 protease inhibitor cocktail (Roche)). 20 µg of protein was subjected to electrophoresis, and then transferred to a nitrocellulose filter (Amersham).…”

An overview of AVF maturation and endothelial dysfunction in an advanced renal failure

“…Furthermore, Dardik et al [53] has revealed that vascular response seems to be significantly influenced by the exact type of shear stress. For instance, matrix metalloproteinase up-regulation, higher proliferation of cells, and a pro-inflammatory environment can be caused by oscillatory shear stress [54]. On the other hand, normal dilatation and endothelial stability are the outcomes of laminar shear stress [55].…”

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

“…Oscillatory shear stress induces VSMC migration by increasing the expression of MMP-2 and MMP-9 and decreasing plasminogen activator inhibitor-1 (PAI-1) expression [134,135]. In vascular grafts, disturbed flow provides favourable conditions for VSMC proliferation with low shear stress, which may explain, in part, why intimal hyperplasia and atherosclerotic lesions develop preferentially in slow-flow regions [136].…”