Simvastatin and Losartan Differentially and Synergistically Inhibit Atherosclerosis in Apolipoprotein E-/- Mice.
10.4070/kcj.2012.42.8.543
- Author:
Bok Soo LEE
1
;
Jin Yong CHOI
;
Joo Yun KIM
;
Seul Hee HAN
;
Jeong Euy PARK
Author Information
1. Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Atherosclerosis;
Losartan;
Simvastatin;
Mice, knockout;
Models, animal
- MeSH:
Angiotensin Receptor Antagonists;
Animals;
Apolipoproteins;
Atherosclerosis;
Azo Compounds;
Cardiovascular Diseases;
Diet;
Humans;
Losartan;
Macrophages;
Mice;
Mice, Knockout;
Models, Animal;
Muscle, Smooth;
Myocytes, Smooth Muscle;
Simvastatin;
Sinus of Valsalva
- From:Korean Circulation Journal
2012;42(8):543-550
- CountryRepublic of Korea
- Language:English
-
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 AND METHODS: 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.
