Chapter 21 - Mechanisms of calcification in the aortic wall and aortic valve

Abstract

Cardiovascular calcification is a leading predictor of and contributor to acute cardiovascular events and aortic wall stiffening. With no approved drug therapies to prevent or regress calcification, understanding the pathophysiological mechanisms associated with ectopic calcification is the basis for development of effective therapeutic strategies. Calcification of the aortic wall and valve is an active process that contributes to the occurrence of cardiovascular events, such as myocardial infarction, heart failure, and stroke. Hemodynamic forces are integral to maintaining a healthy vasculature; however, they can disturb the physiology of the cardiovascular system during disease states. Vascular endothelial cells can perceive and translate mechanical stimuli generated by blood flow to biochemical signals that modulate gene expression, protein synthesis, cell proliferation, differentiation, and migration by smooth muscle cells (SMCs) and valvular interstitial cells (VICs). Mechanical stress causes alterations of SMCs and VICs phenotype lead to increasing local inflammation that culminates in calcium deposition. This chapter will focus on the general mechanisms of aortic wall calcification, with an emphasis on mechanisms by which cardiovascular cells respond to hemodynamic factors, leading to calcification of the aortic wall and aortic valve.