BMP signaling in vascular calcification: A study on the probable pathways of inhibition

Vascular calcification causes more than 20,000 deaths each year, and the aortic valve is the most commonly affected due to it. It leads to mineral deposition in the aortic side of heart valves which leads to stenosis, – characterized by the narrowing of the vessel lumen, and often requires surgical valve replacement. Initially this condition was attributed to a passive process of “wear and tear” of the heart but recent studies have confirmed the presence of inflammation, infiltration of lipids, and presence of bone related proteins in affected valves. In human-beings, the aortic valve is a trileaflet structure which is generally divided into an outer layer of Valve Endothelial Cells (VECs) and three internal layers of Valve Interstitial Cells (VICs), less than 5 % of smooth muscle cells and myofibroblasts. Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor (TGFβ) Superfamily, which play inevitable roles in the maintenance and repair of bone and other tissues in an adult. BMPs were first identified to be potential inducers of ectopic bone formation, after being injected subcutaneously in rats. With respect to the calcification of the heart tissue, their fundamental effect is seen in the smooth muscle cells, which gradually change their phenotype from vascular to synthetic, and lay down the ground for subsequent calcification. Common to the variant processes of vascular calcification is a prominent involvement of BMP-2 paracrine signaling. It may also be noted that the processes of bone formation and atherosclerosis are similar to each other in many instances and hence bring about the possibility of common pathways to combat the two similar conditions. This review article focuses on the effects of BMPs in the control and development of vascular calcification, and the probable pathways that may interfere with or augment this BMP-induced vascular calcification process.