Matrix metalloproteinase-2 deficiency impairs aortic atherosclerotic calcification in ApoE-deficient mice

Objective: Matrix metalloproteinases (MMPs) have been implicated in the process of vascular calcification. However, the exact roles of individual MMPs in vascular calcification are poorly understood. To study the putative role of MMP-2 in atherogenic calcification in vivo and in vitro, we investigate whether or not MMP-2 deficiency affects aortic atherosclerotic calcification in apolipoprotein E-deficient (Apoe(-/-)) mice and cultured smooth muscle cell (SMC) calcification.

Methods and results: The area of calcified lesions in aortic intima was significantly larger in MMP-2(+/+) Apoe(-/-) mice at 45 and 60 weeks of age than in MMP-2(-/-) Apoe(-/-) mice. In these aortic calcified atherosclerotic lesions, the expression of type II collagen, osteoprotegerin, bone morphogenetic protein (BMP)-2 and osteocalcin which are chondrocyte maker and bone-related proteins, was observed. MMP-2 deficiency reduced BMP-2 and osteocalcin expression in aortae in Apoe(-/-) mice at 30 weeks and 45-60-weeks-old, respectively. The expressions of MMP-2 and that of α-SMC actin were observed in chondrocyte-like cells of calcified lesions. Beta-glycerophosphate administration induced calcium deposition in MMP-2(+/+) aorta-derived cultured SMCs, and this calcium deposition was significantly suppressed in MMP-2(-/-) aorta-derived cultured SMCs.

Conclusions: These results suggest that MMP-2 may contribute to the mechanisms of calcification associated with atherosclerosis.