title: Simvastatin and losartan differentially and synergistically inhibit atherosclerosis in apolipoprotein e(-/-) mice.
abstract: OBJECTIVE
  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.
  
  
  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 µm(2) vs. HFHC plus losartan; 255965.3±74057.7 µm(2), 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 µm(2) vs. HFHC plus simvastatin; 120556.0±39282.8 µm(2), p<0.05) and 44% (HFHC; 183575.6±43211.2 µm(2) vs. HFHC plus simvastatin and losartan; 103229.0±8473.3 µm(2), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Bok-Soo
authors.initials: BS
authors.lastname: Lee
authors.forename: Jin Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Joo Yun
authors.initials: JY
authors.lastname: Kim
authors.forename: Seul Hee
authors.initials: SH
authors.lastname: Han
authors.forename: Jeong Euy
authors.initials: JE
authors.lastname: Park