Role of shear stress and stretch in vascular mechanobiology

Abstract

Blood vessels are under constant mechanical loading from blood pressure and flow which cause internal stresses (endothelial shear stress and circumferential wall stress, respectively). The mechanical forces not only cause morphological changes of endothelium and blood vessel wall, but also trigger biochemical and biological events. There is considerable evidence that physiologic stresses and strains (stretch) exert vasoprotective roles via nitric oxide and provide a homeostatic oxidative balance. A perturbation of tissue stresses and strains can disturb biochemical homeostasis and lead to vascular remodelling and possible dysfunction (e.g. altered vasorelaxation, tone, stiffness, etc.). These distinct biological endpoints are caused by some common biochemical pathways. The focus of this brief review is to point out some possible commonalities in the molecular pathways in response to endothelial shear stress and circumferential wall stretch.

Figure 1.

A schematic diagram of cellular responses from the flow and pressure overload. The next level biochemical pathways induced by the wall shear stress and circumferential stretch are depicted in the graph. Two cell types, endothelial and SMC are included in the pathway. In the graph, solid arrows indicate activation while dash blunts indicate negative regulations.

Figure 2.

Vasodilations induced by forward or reverse flow conditions. This graph is revised from our previous work [28] and summarizes the degree of dilation as the function of flow rate. (a) Vessel dilation in forward flow condition (from proximal to distal) and (b) that in the reversal flow condition (from distal to proximal). Several superoxide pathway inhibitors were included in the experiment: solid line with filled black square, apocynin, a superoxide scavenger and NADPH oxidase inhibitor; dashed line with open triangle, gp91ds-tat, a NADPH oxidase inhibitor; small dashed line with filled black diamond, oxypurinol, a xanthine oxidase inhibitor; dashed-dotted line with open diamond, rotenone, a mitochondrial oxidase inhibitor; grey solid line with open circle, control. This graph highlights that reverse flow induces rate-dependent dilation in the similar degree as compared with forward flow in the presence of superoxide scavenger (apocynin) or a NADPH oxidase inhibitor (gp91ds-tat). The data suggest that flow direction and NADPH oxidase are essential to mediate the degree of dilation.