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

文献类型:期刊论文

作者Liang, C; Wu, ZG; Ding, J; Jiang, JF; Huang, GZ; Du, RZ; Ge, JB
刊名ACTA PHARMACOLOGICA SINICA
出版日期2004-11
卷号25期号:11页码:1426-1432
关键词losartan metalloproteinases angiotensin II atherosclerosis peritoneal macrophages reverse transcriptase polymerase chain reaction Western blotting
ISSN号1671-4083
文献子类Article
英文摘要AIM: To explore whether the angiotensin II (Ang II) receptor 1 (AT(1)) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D(3) 600 kU(.)kg(-1) -month(-1) and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 mg(.)kg(-1.)d(-1) was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10 mumol/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 mumol/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 AT(2) receptor 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.
WOS关键词SMOOTH-MUSCLE-CELLS ; NF-KAPPA-B ; CHOLESTEROL-FED RABBITS ; TYPE-1 RECEPTOR ; CONVERTING ENZYME ; TISSUE INHIBITOR ; BLOCKADE ; ARTERY ; ATHEROGENESIS ; INFLAMMATION
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:1847683
WOS记录号WOS:000224947400007
出版者SHANGHAI INST MATERIA MEDICA
源URL[http://119.78.100.183/handle/2S10ELR8/273996]  
专题中国科学院上海药物研究所
通讯作者Wu, ZG
作者单位1.Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai 200032, Peoples R China
2.Mil Med Univ 2, Changzheng Hosp, Dept Cardiol, Shanghai 200003, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
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Liang, C,Wu, ZG,Ding, J,et al. Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin II-stimulated macrophages[J]. ACTA PHARMACOLOGICA SINICA,2004,25(11):1426-1432.
APA Liang, C.,Wu, ZG.,Ding, J.,Jiang, JF.,Huang, GZ.,...&Ge, JB.(2004).Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin II-stimulated macrophages.ACTA PHARMACOLOGICA SINICA,25(11),1426-1432.
MLA Liang, C,et al."Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin II-stimulated macrophages".ACTA PHARMACOLOGICA SINICA 25.11(2004):1426-1432.

入库方式: OAI收割

来源:上海药物研究所

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