Rosuvastatin inhibits MMP-2 expression and limits the progression of atherosclerosis in LDLR-deficient mice.
OBJECTIVE
Statins have been shown to reduce morbidity and mortality of coronary heart disease (CHD). Matrix metalloproteinases (MMPs) have been found to be involved in atherosclerotic plaque growth and instability. Rosuvastatin may inhibit the secretion of MMP-2 and MMP-9 from vascular smooth muscle cells and macrophages in vitro. The present study investigated the effects of rosuvastatin on the progression of atherosclerosis and the expression of MMP-2/-9 in LDLR-deficient mice.


METHODS
LDLR-deficient mice were included in rosuvastatin group and control group on a high-fat and high-cholesterol diet. After 12 weeks, we randomly sacrificed and examined the atherosclerotic lesion area in aortic artery and aortic sinus and levels of plasma lipid, glucose and insulin and expression of MMP-2 and MMP-9 in the atherosclerotic plaques.


RESULTS
Atherosclerotic lesion area was significantly decreased in rosuvastatin group vs. control group. Meanwhile, levels of plasma total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and oxidized (ox)LDL in the rosuvastatin group were decreased as well as MMP-2 and MMP-9 expression in aortic arch with gelatin zymography and the production of MMP-2 in the aortic sinus through immunohistochemical methods. Levels of plasma high-density lipoprotein cholesterol (HDL-C), glucose and insulin were also decreased in rosuvastatin group but failed to achieve statistical significance compared with control group. Interestingly, we found that the value of HDL-C/TC ratio was increased in rosuvastatin group.


CONCLUSIONS
Rosuvastatin inhibits the expression of MMP-2/-9 and limits the progression of atherosclerosis in LDLR-deficient mice. This may be one of the pathways of rosuvastatin on atherosclerosis through which rosuvastatin induced its benefit to the therapy of coronary heart disease (CHD).
Guo
Hangyuan
H
Department of Cardiology, Shaoxing People's Hospital, Zhejiang, China. ghangyuan@hotmail.com
Shi
Yafei
Y
Liu
Longbin
L
Sun
Aijing
A
Xu
Fukang
F
Chi
Jufang
J
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology; D002784:Cholesterol / Q000097:blood; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000235:genetics; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000097:blood
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D061965:Matrix Metalloproteinase Inhibitors; D011743:Pyrimidines; D011973:Receptors, LDL; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; D005947:Glucose