Telmisartan exerts antiatherosclerotic effects by activating peroxisome proliferator-activated receptor-γ in macrophages.
Arterioscler Thromb Vasc Biol
; 31(6): 1268-75, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21474824
ABSTRACT
OBJECTIVE:
Telmisartan, an angiotensin type I receptor blocker (ARB), protects against the progression of atherosclerosis. Here, we investigated the molecular basis of the antiatherosclerotic effects of telmisartan in macrophages and apolipoprotein E-deficient mice. METHODS ANDRESULTS:
In macrophages, telmisartan increased peroxisome proliferator-activated receptor-γ (PPARγ) activity and PPAR ligand-binding activity. In contrast, 3 other ARBs, losartan, valsartan, and olmesartan, did not affect PPARγ activity. Interestingly, high doses of telmisartan activated PPARα in macrophages. Telmisartan induced the mRNA expression of CD36 and ATP-binding cassette transporters A1 and G1 (ABCA1/G1), and these effects were abrogated by PPARγ small interfering RNA. Telmisartan, but not other ARBs, inhibited lipopolysaccharide-induced mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α, and these effects were abrogated by PPARγ small interfering RNA. Moreover, telmisartan suppressed oxidized low-density lipoprotein-induced macrophage proliferation through PPARγ activation. In apolipoprotein E(-/-) mice, telmisartan increased the mRNA expression of ABCA1 and ABCG1, decreased atherosclerotic lesion size, decreased the number of proliferative macrophages in the lesion, and suppressed MCP-1 and tumor necrosis factor-α mRNA expression in the aorta.CONCLUSION:
Telmisartan induced ABCA1/ABCG1 expression and suppressed MCP-1 expression and macrophage proliferation by activating PPARγ. These effects may induce antiatherogenic effects in hypertensive patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzimidazóis
/
Benzoatos
/
PPAR gama
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Bloqueadores do Receptor Tipo 1 de Angiotensina II
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Aterosclerose
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Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article