Mechanisms and clinical consequences of vascular calcification

Abstract

Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health.

Keywords: therapeutic strategies; vascular calcification; vascular smooth muscle cells.

Figure 1

Extensive calcific aortic valve stenosis in the valve leaflets of a patient undergoing valve replacement surgery.

Figure 2

Calcification of murine vascular smooth muscle cells cultured in vitro in the presence of (A) high phosphate (2.5 mM) compared to (B) control medium.

Figure 3

Diagramatic representation of selected regulatory factors and their potential roles in vascular calcification.

Figure 4

Positive and negative regulators of vascular calcification.

Figure 5

Medial calcification of the aorta due to depressed levels of the calcification inhibitor pyrophosphate in the (A) Enpp1-null mouse, compared to (B) wild-type control.