Plaque-prone hemodynamics impair endothelial function in pig carotid arteries

Abstract

Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that low shear stress combined with cyclic reversal of flow direction (oscillatory shear stress) affects the endothelial cells and may lead to an initiation of plaque development. The aim of the study was to analyze the effect of hemodynamic conditions in arterial segments perfused in vitro in the absence of other stimuli. Left common porcine carotid segments were mounted into an ex vivo arterial support system and perfused for 3 days under unidirectional high and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) and oscillatory shear stress (0.3 +/- 3 dyn/cm(2)). Bradykinin-induced vasorelaxation was drastically decreased in arteries exposed to oscillatory shear stress compared with unidirectional shear stress. Impaired nitric oxide-mediated vasodilation was correlated to changes in both endothelial nitric oxide synthase (eNOS) gene expression and activation in response to bradykinin treatment. This study determined the flow-mediated effects on native tissue perfused with physiologically relevant flows and supports the hypothesis that oscillatory shear stress is a determinant factor in early stages of atherosclerosis. Indeed, oscillatory shear stress induces an endothelial dysfunction, whereas unidirectional shear stress preserves the function of endothelial cells. Endothelial dysfunction is directly mediated by a downregulation of eNOS gene expression and activation; consequently, a decrease of nitric oxide production and/or bioavailability occurs.

Effects of posture on shear rates in human brachial and superficial femoral arteries

“…Based on these data, we speculate that lower resting SRs in the superficial femoral compared with the brachial arteries produce a proatherogenic environment through the heterogeneous expression of eNOS, VCAM-1, and ICAM-1. Our findings of higher OSIs in the superficial femoral compared with the brachial arteries are also of interest relative to in vitro data demonstrating that oscillatory shear initiates a proatherogenic environment through the downregulation of eNOS (8,12,40,41) and upregulation of both VCAM-1 (5) and ICAM-1 (11). We recognize that the oscillatory shear patterns applied to cultured endothelial cells are unlike those currently reported in the brachial and superficial femoral arteries and that this limits the ability to draw direct inferences from these in vitro studies to our current in vivo results.…”

Mechanistic Analysis of Nonoxygenated Hypothermic Machine Perfusion’s Protection on Warm Ischemic Kidney Uncovers Greater eNOS Phosphorylation and Vasodilation

“…Here again, their mRNA levels were not significantly different from the CTL group ( Figure S1A) and there was no significant machine or solution effect ( Figure S1B). We also measured the expression levels of iNOS, another source of NO, and confirmed it was not affected by MP ( Figure S2) MP increased cortical eNOS phosphorylations at the end of preservation Decreases in bloodflow reduce NO production by decreasing eNOS phosphorylation on the activating serine residues (28). As there was no machine effect on eNOS expression, we postulated that MP modulated eNOS phosphorylation.…”

Altered resting hemodynamics in lower-extremity arteries of individuals with spinal cord injury

“…Specifically, oscillatory shear with blood flow reversal exerts effects through increased expression of adhesion molecules, monocyte adhesion, 15,17,26 increased superoxide production, 16 and impaired endothelial function. 27 Therefore, for individuals with SCI the reduction in oscillatory shear index suggests that the lower-extremity conduit arteries of these individuals contain an additional key component of an atheroprotective hemodynamic environment. Several factors could explain the differences in oscillatory shear index between SCI and able-bodied controls.…”