Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

• 来源期刊: 中国药理学报（英文版）
• 关键词: losartan metalloproteinases angiotensin Ⅱ atherosclerosis peritoneal macrophages reverse transcriptase polymerase chain reaction Western blotting
• 年，卷（期）: 2004,（11）
• 页码范围: 1426-1432
• 页数: 7页
• 语种: 英文

摘要

AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto induce experimental atheroma. Then either placebo or losartan 50 mg.kg-1.d-1 was administered in rats for another2 months. In vitro, the effect of losartan 0.1-10 μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang Ⅱ-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P＜0.05; MMP-9,10527±1002 vs 14623±2462, P＜0.01). In cultured rat peritoneal macrophages, Ang Ⅱ 0.1 μmol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner(P＜0.01). But the AT2receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang Ⅱ bioactivity.