Matrix metalloproteinases in medial arterial calcification: potential mechanisms and actions

Arterial calcification is now understood to be an actively regulated process with promoters and inhibitors similar to those seen remodeling bone. It occurs in two distinct forms involving either the atherosclerotic intimal or the media. The amount of calcification found in the tibial arteries of the lower extremity is a better predictor of amputation than atherosclerosis risk factors and the ankle brachial index. We and others have recently demonstrated that matrix metalloproteinases (MMPs) play a critical role in the development of experimental arterial calcification in rodent models. The mechanisms by which MMPs may regulate arterial calcification, however, are not completely understood. While MMPs have traditionally been thought to function primarily in the degradation of extracellular matrix molecules, recent data suggest that MMPs may also function as important regulators of matrix biology, inflammation, and osteogenesis. In this review, we will examine recent data on the potential mechanisms by which MMPs may function in the control of arterial calcification.