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


CONCLUSIONS
Heparin can inhibit the production of MMP-2 in the atherosclerotic lesions and improve the atherosclerotic lesions in LDLr(-/-) mice.
Guo
Hangyuan
H
Department of Cardiology, Shaoxing People's Hospital, Zhejiang, China. ghangyuan@hotmail.com
Xu
Fukang
F
Sun
Aijing
A
Liu
Longbin
L
Shi
Yafei
Y
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating; D006493:Heparin / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D002317:Cardiovascular Agents; D008076:Cholesterol, HDL; D011973:Receptors, LDL; D014280:Triglycerides; D006710:Homocysteine; D006493:Heparin; D002784:Cholesterol; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse