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Atherosclerosis ; 217(1): 90-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21481872

RESUMO

OBJECTIVE: Statins reduce atherosclerosis, but it is controversial whether they suppress abdominal aortic aneurysm (AAA) expansion. We hypothesized that statins (rosuvastatin and atorvastatin) would attenuate angiotensin II (AngII)-induced atherosclerosis and AAA. METHODS AND RESULTS: Sixty apoE-/- male mice fed a normal diet were administered with either rosuvastatin (10mg/kg/day) or atorvastatin (20mg/kg/day) through drinking water for 1 week prior to initiating 28-day AngII infusion (1000 ng/kg/min). Statins administration led to therapeutic serum concentrations of drugs. Administration of either rosuvastatin or atorvastatin exerted no significant effect on AngII-induced expansion of suprarenal diameter or area. However, atorvastatin significantly reduced AngII-augmented atherosclerotic lesion areas in intimas of both aortic arches and cross-sections of aortic roots (P<0.001). Atherosclerosis was attenuated independent of reductions in serum total cholesterol concentrations. Although serum MCP-1 and MIF concentrations were not changed by either statins, atorvastatin administration increased PPAR-α and -γ mRNA abundances and decreased NF-κB p50, p65, MCP-1 and TNF-α mRNA abundances in atherosclerotic lesions. CONCLUSIONS: This study demonstrated both statins failed to suppress AngII-induced AAA. In contrast, atorvastatin reduced AngII-induced atherosclerosis associated with no change in serum inflammatory markers but a shift to upregulation of anti-inflammatory status in lesions.


Assuntos
Angiotensina II/metabolismo , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ração Animal , Animais , Anti-Inflamatórios/farmacologia , Aorta/patologia , Aneurisma da Aorta Abdominal/metabolismo , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Atorvastatina , Pressão Sanguínea , Fluorbenzenos/farmacologia , Regulação da Expressão Gênica , Ácidos Heptanoicos/farmacologia , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pirimidinas/farmacologia , Pirróis/farmacologia , Rosuvastatina Cálcica , Sulfonamidas/farmacologia
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