Mechanotransduction in vascular physiology and atherogenesis

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Abstract
Fluid shear stress from blood flow and circumferential stretch of vessel walls from blood pressure are important regulatory factors that control the morphogenesis and physiology of blood vessels. However, atherosclerosis initiates at regions of arteries that, owing to vessel anatomy, develop disturbances in flow patterns. Mechanical forces from blood flow are exerted on many different structural elements in the cell. A number of these might transduce forces into biochemical signals that regulate cellular responses. Disturbed fluid shear stress activates the vascular endothelium to initiate atherosclerosis, mainly because cells cannot adapt to these flow patterns and cannot downregulate signalling pathways. Changes in gene expression and the endothelial extracellular matrix help entrain the activated state to cause life-long chronic inflammation. Systemic risk factors, such as high cholesterol and blood pressure, synergize with disturbed flow to promote the progression of atherosclerosis. These ideas suggest that atherosclerosis arises because the normal physiological responses to laminar flow have unintended consequences in the face of disturbed flow.