Interactive and Multifactorial Mechanisms of Calcific Vascular and Valvular Disease

Abstract

Calcific vascular and valvular disease (CVVD) is widespread and has major health consequences. Although coronary artery calcification has long been associated with hyperlipidemia and increased mortality, recent evidence suggests that its progression is increased in association with cholesterol-lowering HMG-CoA reductase inhibitors ('statins') and long-term, high-intensity exercise. A nationwide trial showed no cardiovascular benefit of vitamin D supplements. Controversy remains as to whether calcium deposits in plaque promote or prevent plaque rupture. CVVD appears to occur through mechanisms similar to those of intramembranous, endochondral, and osteophytic skeletal bone formation. New evidence implicates autotaxin, endothelial-mesenchymal transformation, and microRNA and long non-coding RNA (lncRNA) as novel regulatory factors. New therapeutic options are being developed.

Keywords: atherosclerosis; bone; calcification; cardiovascular; valvular disease.

Figure 1.. Changes in aortic valve cusps in aortic stenosis.

Fibrocalcific changes in the normally thin cusps reduce the size of the opening and blood flow. This figure was created using BioRender (https://biorender.com/).

Figure 2.. Distribution of rupture stress amplitude.

Theoretical analyses showing the degree of rupture (von Mises) stress (scaled by color) in a hypothetical soft tissue in the vicinity of a hypothetical rigid deposit (black circle), which is stretched along the horizontal axis. Rupture risk is greatly increased (red) on the edges facing the direction of pull and reduced (blue) at the perpendicular edges.