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Updated: May 15, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Matrix metalloproteinase-2 deficiency impairs aortic atherosclerotic calcification in ApoE-deficient mice
Takeshi Sasaki1, Kae Nakamura, Kumiko Sasada
1Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, 1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. tsasaki@hama-med.ac.jp
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.
Insights
Matrix metalloproteinase-2 (MMP-2) deficiency significantly reduces aortic calcification in atherosclerosis-prone mice and inhibits calcium deposition in cultured smooth muscle cells. These findings highlight MMP-2
Area of Science:
- Cardiovascular Biology
- Vascular Biology
- Matrix Biology
Background:
- Matrix metalloproteinases (MMPs) are implicated in vascular calcification.
- The specific roles of individual MMPs, particularly MMP-2, in vascular calcification remain unclear.
Purpose of the Study:
- To investigate the role of MMP-2 in atherogenic calcification.
- To determine the effect of MMP-2 deficiency on aortic atherosclerotic calcification in apolipoprotein E-deficient (Apoe(-/-)) mice.
- To assess the impact of MMP-2 deficiency on smooth muscle cell (SMC) calcification in vitro.
Main Methods:
- Utilized apolipoprotein E-deficient (Apoe(-/-)) mice with and without MMP-2 (MMP-2(+/+) and MMP-2(-/-)) to study aortic calcification.
- Analyzed calcified lesion area and expression of chondrocyte and bone-related proteins in aortae.
- Investigated beta-glycerophosphate-induced calcium deposition in cultured SMCs derived from MMP-2(+/+) and MMP-2(-/-) aortae.
Main Results:
- MMP-2(+/+) Apoe(-/-) mice exhibited significantly larger calcified aortic lesions compared to MMP-2(-/-) Apoe(-/-) mice.
- MMP-2 deficiency reduced bone morphogenetic protein (BMP)-2 and osteocalcin expression in aortae.
- Beta-glycerophosphate-induced calcium deposition in cultured SMCs was significantly suppressed in the absence of MMP-2.
Conclusions:
- MMP-2 plays a role in the mechanisms of vascular calcification associated with atherosclerosis.
- MMP-2 deficiency confers protection against aortic calcification in a mouse model of atherosclerosis.
- MMP-2 contributes to the calcification process in vascular smooth muscle cells.
