Sitting and endothelial dysfunction: the role of shear stress

Abstract

Sedentary activity is a modifiable life-style behavior and a key component in the etiology of atherosclerotic cardiovascular disease (ACVD). US adults and children spend more than half their waking time in sedentary pursuits. Sedentary activity has been shown to result in impaired insulin sensitivity, impaired metabolic function and attenuated endothelial function, which are classic markers of ACVD. Sedentary activity is defined as 'sitting without otherwise being active.' This behavior promotes reduced muscular activity of the lower extremities which decreases leg blood flow, increases blood pooling in the calf, augments mean arterial pressure, and deforms arterial segments resulting in low mean shear stress (SS). SS activates distinct physiological mechanisms which have been proposed to be protective against ACVD; specifically through a SS-induced endothelium-derived nitric oxide mechanism. Reduced bioavailability of nitric oxide creates a pro-oxidant milieu resulting in increased oxidative stress. There is sufficient evidence which demonstrates that endothelial function is attenuated in the presence of oxidative stress. Sedentary activity results in low SS in the lower extremities which may result in increased oxidative stress and impaired endothelial function. This review furthers the use of sitting as model to study the effects of inactivity, discusses possible physiological mechanisms and suggests future directions.

Figure 1

Continuum of physical activity.

Figure 2A

Normal functioning of the shear stress, acetylcholine and insulin mediated NO mechanism in and around the endothelial cell. In the presence of laminar shear stress, insulin and acetylcholine, nitric oxide is produced from L-Arginine. Nitric oxide functions as an anti-oxidant molecule. It also performs the functions of anti-coagulation, anti-adhesion, anti-fibrinolysis and vasodilation in the endothelial environment

Figure 2B

Low, oscillatory or turbulent shear stress results in endothelial injury and release of endothelial microparticles. Altered shear stress directly and indirectly impairs the nitric oxide bioavailability resulting in oxidative stress and decline in anti-atherosclerotic functions thus resulting in endothelial dysfunction and pro-atherosclerotic environment. Crossed out ‘shear stress’ implies non-laminar shear stress. ‘X’ marks represent decline in or blocking of a particular function.