Cellular mechanics and gene expression in blood vessels

Abstract

Blood vessels are permanently subjected to mechanical forces in the form of stretch, encompassing cyclic mechanical strain due to the pulsatile nature of blood flow, and shear stress. Alterations in stretch or shear stress invariably produce transformations in the vessel wall that will aim to accommodate the new conditions and to ultimately restore basal levels of tensile stress and shear stress. Vascular cells are equipped with numerous receptors that allow them to detect and respond to the mechanical forces generated by pressure and shear stress. The cytoskeleton and other structural components have an established role in mechanotransduction, being able to transmit and modulate tension within the cell via focal adhesion sites, integrins, cellular junctions and the extracellular matrix. Beyond the structural modifications incurred, mechanical forces can also initiate complex signal transduction cascades leading to functional changes within the cell. Many intracellular pathways, including the MAP kinase cascade, are activated by flow or stretch and initiate, via sequential phosphorylations, the activation of transcription factors and subsequent gene expression.