Abstract: AIM: To study the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin on MCP-1 expression and macrophages infiltration in pressure overload-induced myocardial fibrosis in rats with hypertension induced by abdominal aortic coarctation and further clarify the underlying mechanism of the treatment. METHODS: Pressure overload-induced rat model was established by abdominal aorta constriction (AC). Eighteen SD rats were divided randomly into sham group, AC group and simvastatin group. At the ending of observation, mean arterial blood pressure (MBP) was measured by carotid artery intubation, and ratio of ventricle mass to body weigh (LVW BW) was calculated. Myocardial interstitial fibrosis and perivascular fibrosis were evaluated by PAS. Immunohistochemistry was used on myocardium for ED-1 which was a marker of macrophage. MCP-1 mRNA and protein expression levels in myocardium were determined with reverse transcription polymerase chain reaction (RT-PCR) and ELISA, respectively. RESULTS: MBP, LVW BW, MCP-1 protein and mRNA expression in both AC group and simvastatin group were significantly higher than those in sham group (P<0.05 or P<0.01). Collagen volume fraction (CVF) and perivascular circumferential area (PCVA) , ED-1 positive cells in AC group were increased significantly compared with sham group (P<0.01). LVW BW, CVF, PCVA, ED-1 positive cells, MCP-1 protein and mRNA expression in simvastatin group were significantly lower than those in the AC group (P<0.01). CONCLUSION: Simvastatin prevents pressure overload-induced rat’ s myocardial fibrosis, which is associated with the reduction of MCP-1 in myocardium and interstitial macrophage infiltration.

Key words: monocyte chemoattractant protein-1, simvastatin, macrophage, myocardial fibrosis