Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin II-stimulated macrophages.
Acta Pharmacol Sin
; 25(11): 1426-32, 2004 Nov.
Article
em En
| MEDLINE
| ID: mdl-15525463
ABSTRACT
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 rats were ip injected a single dose of vitamin D3 600 kU x kg(-1) x month(-1) and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 mg x kg(-1) x d(-1) was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10 micromol/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 micromol/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 AT2 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arteriosclerose
/
Macrófagos Peritoneais
/
Losartan
/
Metaloproteinase 2 da Matriz
/
Metaloproteinase 9 da Matriz
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article