Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype

Abstract

Current evidence indicates that the ability of physical activity to sustain a normal phenotype of arterial endothelial cells (ECs) plays a central role in the beneficial effects of exercise (Ex) on atherosclerotic disease. Here we evaluate the strength of evidence that shear stress (SS) and/or circumferential wall stress (stretch) are the primary signals, produced by bouts of Ex, that signal altered gene expression in arterial ECs, thereby resulting in a less atherogenic EC phenotype. Current literature indicates that SS is a signal for expression of antiatherogenic genes in cultured ECs, in ECs of isolated arteries, and in ECs of arteries in intact animals. Furthermore, SS levels in the arteries of humans during Ex are in the range that produces beneficial changes. In contrast, complex flow profiles within recirculation zones and/or oscillatory flow patterns can cause proatherogenic gene expression in ECs. In vivo evidence indicates that Ex decreases oscillatory flow/SS in some portions of the arterial tree but may increase oscillatory flow in other areas of the arterial tree. Circumferential wall stress can increase expression of some beneficial EC genes as well, but circumferential wall stress also increases production of reactive oxygen species and increases the expression of adhesion factors and other proatherogenic genes. Interactions of arterial pressure and fluid SS play an important role in arterial vascular health and likely contribute to how Ex bouts signal changes in EC gene expression. It is also clear that other local and circulating factors interact with these hemodynamic signals during Ex to produce the healthy arterial EC phenotype. We conclude that available evidence suggests that exercise signals formation of beneficial endothelial cell phenotype at least in part through changes in SS and wall stretch in the arteries.

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

“…Increase in cardiac output could alter mean fluid shear and affect NO production, as occurs with exercise and as others have reported (15,16,28,31,37). We have not directly measured cardiac output in rats in response to pG z .…”

“…In intact animals, laminar shear stress has been thoroughly investigated (19,33,51). However, there has been much less study of pulsatile shear stress alone in intact animals, with the exception of extracorporeal circulation, owing to the paucity of modalities to induce pulsatile shear stress in vivo (31,54). Nakano et al (41), in an extracorporeal model of pulsatile shear stress, found that eNOS activation is largely caused by tyrosine kinase-sensitive activation.…”

Impact of 2‐Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men

“…Previous studies provide strong evidence that (repeated) elevations in antegrade or mean SR represent a potent hemodynamic stimulus that acutely and chronically alters vascular function and structure 1, 5, 6, 7, 8, 9, 10. As a logical follow‐up study from initial findings that acute elevation in retrograde shear induces impairment in endothelial function,2 this study aimed to assess the effect of chronic (ie, 2 weeks) manipulation of retrograde SR in humans in vivo.…”

“…Typically, shear stress follows a cyclic pattern, directed towards the periphery during systole (antegrade shear) and, under some circumstances, directed backwards to the heart during diastole (retrograde shear) 4. Elevations in antegrade shear stress are associated with potentially beneficial effects on the vessel wall 1, 5, 6, 7, 8, 9, 10. In contrast, elevation in retrograde shear stress may be potentially detrimental 2, 10, 11.…”

Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

“…Although the focus of this study is to understand the fundamental mechanobiology of endothelial adaptation, our results may shed some light on the effects of physical exercise on endothelial cells. Proposed 20 years ago by Laughlin and McAllister (22), it is well accepted that shear stress is a primary signal in mediating exercise-induced vascular adaptation and thus is a key player in the prevention of endothelial dysfunction and cardiovascular diseases (23). Physical exercise increases heart rate and stroke volume, leading to an increase in both the magnitude and the frequency of local shear stress.…”