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![]() |
刊名 | ACTA PHARMACOLOGICA SINICA
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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 |
推荐引用方式 GB/T 7714 | 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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