Simvastatin and Losartan Differentially and Synergistically Inhibit Atherosclerosis in Apolipoprotein E-/- Mice
Korean Circulation Journal
;
: 543-550, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-147046
ABSTRACT
BACKGROUND AND OBJECTIVES:
Since statins and angiotensin receptor blockers are a frequently prescribed combination in patients with atherosclerotic cardiovascular diseases, we tested the interactive effects of simvastatin and losartan on atherosclerosis in apolipoprotein E (apoE)-/- mice. MATERIALS ANDMETHODS:
Apolipoprotein E-/- mice were fed a high-fat, high-cholesterol (HFHC) diet for 12 weeks, with and without simvastatin (40 mg/kg) and/or losartan (20 mg/kg). The mice were divided into 5 groups and were fed as follows regular chow (control diet, n=5), HFHC diet (n=6), HFHC diet with losartan (n=6), HFHC diet with simvastatin (n=6), and HFHC diet with both losartan and simvastatin (n=6).RESULTS:
Losartan treatment in apoE-/- mice significantly decreased atherosclerotic lesion areas in whole aortic strips stained with Oil Red O. The plaque area measured at the aortic sinus level was reduced significantly by 17% (HFHC; 346830.9+/-52915.8 microm2 vs. HFHC plus losartan; 255965.3+/-74057.7 microm2, p<0.05) in the losartan-treated group. Simvastatin and simvastatin plus losartan treatments reduced macrophage infiltration into lesions by 33% (HFHC; 183575.6+/-43211.2 microm2 vs. HFHC plus simvastatin; 120556.0+/-39282.8 microm2, p<0.05) and 44% (HFHC; 183575.6+/-43211.2 microm2 vs. HFHC plus simvastatin and losartan; 103229.0+/-8473.3 microm2, p<0.001, respectively). In mice fed the HFHC diet alone, the smooth muscle cell layer in the aortic media was almost undetectable. In mice co-treated with losartan and simvastatin, the smooth muscle layer was more than 60% preserved (p<0.05). Given alone, losartan showed a slightly stronger effect than simvastatin; however, treatment with losartan plus simvastatin induced a greater inhibitory effect on atherosclerosis than either drug given alone. Serum lipid profiles did not differ significantly among the groups.CONCLUSION:
Losartan displayed anti-atherosclerotic effects in apoE-/- mice that were equivalent to or greater than the effects of simvastatin. Combined treatment with these drugs had greater effect than either drug alone.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Apolipoproteínas
/
Seio Aórtico
/
Compostos Azo
/
Doenças Cardiovasculares
/
Camundongos Knockout
/
Losartan
/
Sinvastatina
/
Modelos Animais
/
Miócitos de Músculo Liso
/
Dieta
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Korean Circulation Journal
Ano de publicação:
2012
Tipo de documento:
Artigo
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