Roles of Hemodynamic Forces in Vascular Cell Differentiation

Abstract

The pulsatile nature of blood flow is a key stimulus for the modulation of vascular cell differentiation. Within the vascular media, physiologic stress is manifested as cyclic strain, while in the lumen, cells are subjected to shear stress. These two respective biomechanical forces influence the phenotype and degree of differentiation or proliferation of smooth muscle cells and endothelial cells within the human vasculature. Elucidation of the effect of these mechanical forces on cellular differentiation has led to a surge of research into this area because of the implications for both the treatment of atherosclerotic disease and the future of vascular tissue engineering. The use of mechanical force to directly control vascular cell differentiation may be utilized as an invaluable engineering tool in the future. However, an understanding of the role of hemodynamics in vascular cell differentiation and proliferation is critical before application can be realized. Thus, this review will provide a current perspective on the latest research and controversy behind the role of hemodynamic forces for vascular cell differentiation and phenotype modulation. Furthermore, this review will illustrate the application of hemodynamic force for vascular tissue engineering and explicate future directions for research.

A common mechanism underlies stretch activation and receptor activation of TRPC6 channels

“…Hemodynamic forces, shear stress, and stretch-induced Ca 2ϩ signals are a major determinant of vascular cell morphology and function (12,34). However the gating mechanisms and the mechanical sensors that mediate the response to hemodynamic force have not been clarified.…”

KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium

“…It has been postulated that shear stress, the tangential force exerted by the flowing blood on the vascular endothelial lining, is of prime importance in determining endothelial phenotype. 4,5 Over recent years, the zinc finger transcription factor lung Krüppel-like factor (LKLF/KLF2) has emerged as a prime and pivotal candidate for directly relaying biomechanical shear forces into a gene transcription profile that might determine endothelial phenotype in response to flow. [6][7][8][9][10] We previously demonstrated that KLF2 mRNA and protein levels are substantially and uniquely induced by prolonged steady or pulsatile laminar flow both in vitro and in vivo.…”

Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells

“…Similarly, in PDGF-BB -/-mice, SMCs are not recruited around vessels, and pericytes are aberrantly located (13). Beyond cytokines, mechanical forces contribute to SMC development and postnatal maturation, as cyclical strain results in upregulation of contractile proteins within SMCs along with increases in ECM secretion (14).…”