Heparin inhibits the production of matrix metalloproteinase-2 and improves atherosclerosis in LDL receptor-deficient mice

Abstract

Objective: This study aimed to find the effects of heparin on atherosclerosis and the production of matrix metalloproteinase (MMP)-2 in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice.

Methods: Sixteen 7-week-old LDLr(-/-) mice were randomized to receive sterile water or heparin. The levels of total cholesterol, high-density lipoprotein cholesterol, triglyceride and homocysteine were measured. Mean lesions area was calculated as the total atherosclerotic lesions area and expressed as a percentage of total luminal surface area. The lesions area was measured blindly by the same person using computer-assisted image analysis. The expression and localization of the MMP-2 was examined by immunohistochemistry.

Results: All mice exhibited atherosclerotic lesions in the aortic sinus and aortic surface. Total cholesterol was decreased, while high-density lipoprotein cholesterol was increased in heparin compared with that in control group (P=0.001 and 0.002). Triglyceride was not significantly different between the two groups (P=0.92). The amount of atherosclerotic lesions in the aortic surface was 40.5% lower in heparin group than that in the control group (P<0.001). The mean area of atherosclerotic lesions in the aortic sinus was also less in the heparin group than that in the control group. Coincidently, the expression of MMP-2 in the atherosclerotic lesions in the heparin group was 49.3% lower than that in the control group (P<0.001).

Conclusion: Heparin can inhibit the production of MMP-2 in the atherosclerotic lesions and improve the atherosclerotic lesions in LDLr(-/-) mice.