Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, 1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Atherosclerosis. 2013 Mar;227(1):43-50. doi: 10.1016/j.atherosclerosis.2012.12.008. Epub 2012 Dec 19.
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.
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.
These results suggest that MMP-2 may contribute to the mechanisms of calcification associated with atherosclerosis.
基质金属蛋白酶（MMPs）被认为参与了血管钙化的过程。然而，个体 MMP 在血管钙化中的确切作用仍知之甚少。为了研究 MMP-2 在动脉粥样硬化钙化中的潜在作用，我们研究了 MMP-2 缺陷是否会影响载脂蛋白 E 缺陷（Apoe（-/-））小鼠的主动脉粥样硬化钙化和培养的平滑肌细胞（SMC）钙化。
在 45 周和 60 周龄时，MMP-2（+/+）Apoe（-/-）小鼠的主动脉内膜钙化病变面积明显大于 MMP-2（-/-）Apoe（-/-）小鼠。在这些主动脉钙化性动脉粥样硬化病变中，观察到了Ⅱ型胶原、骨保护素、骨形态发生蛋白-2（BMP-2）和骨钙素的表达，这些是软骨细胞标志物和骨相关蛋白。MMP-2 缺陷分别降低了 30 周和 45-60 周龄 Apoe（-/-）小鼠主动脉中 BMP-2 和骨钙素的表达。在钙化病变的软骨样细胞中观察到 MMP-2 和α-SMC 肌动蛋白的表达。β-甘油磷酸钠诱导 MMP-2（+/+）主动脉源性培养的 SMC 中钙沉积，而 MMP-2（-/-）主动脉源性培养的 SMC 中钙沉积显著受到抑制。
这些结果表明，MMP-2 可能参与了与动脉粥样硬化相关的钙化机制。
