Mechanobiology in Cardiovascular Disease Management: Potential Strategies and Current Needs.

Abstract

Mechanical forces are powerful regulators of biology and disease. In the vasculature, the expression of particular cellular phenotypes appears to depend not only on a combination of intrinsic genetically programed biology but also on local hemodynamic environmental factors induced by blood flow (Nerem and Girard, 1990). A major component in the spectrum of forces experienced by cardiovascular tissue is the friction force exerted by the blood flow on the endothelium. Through multiple dedicated receptors, endothelial cells are able to sense the magnitude and directionality of this force and of the resulting wall shear stress (WSS), and to transduce this mechanical signal into biochemical signals, altering in turn cellular function. Interestingly, while physiologic WSS maintains vascular homeostasis (Figure 1A), WSS abnormalities often correlate with disease states (Figure 1B). While hemodynamic pathways have been identified in some cardiovascular pathologies such as calcific aortic valve disease (CAVD) (Butcher et al., 2008), aneurysms (Humphrey et al., 2015), atherosclerosis (Cunningham and Gotlieb, 2005), and intimal hyperplasia (IH) (Haruguchi and Teraoka, 2003), the clinical management of these disorders remains focused on addressing their symptoms via aggressive modalities rather than blocking the flow-induced pathological cascade. As a result, current treatments are often palliative and ignore the driving biological processes. In this context, the elucidation of the cause-and-effect relationships between cardiovascular biology and hemodynamics has the potential to advance the understanding of disease progression and to enable new diagnosis and treatments.