title: Comparison of angiotensin-(1-7), losartan and their combination on atherosclerotic plaque formation in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  Inhibition of the classical renin-angiotensin system (RAS) has been proved to reduce atherosclerosis. Recently, angiotensin-(1-7) [Ang-(1-7)], a new component of RAS, has been shown to attenuate atherosclerosis formation. However, direct comparison of Ang-(1-7) and angiotensin II type 1 receptor blocker (ARB) on atherogenesis is sparse. Here, we investigated whether large dose of Ang-(1-7) and losartan are equivalent or the combination of both is superior in reducing atherosclerotic plaque formation.
  
  
  RESULTS
  In vivo, we established an atherosclerosis model in ApoE-/- mice. All mice were fed a high fat diet during experiments. Mice were divided into control, Ang-(1-7), losartan, Ang-(1-7)+losartan groups for 4 weeks treatment. Ang-(1-7) did not change the blood pressure (BP) levels, while losartan produced a significant decrease in systolic BP. The attenuation of Ang-(1-7) and losartan in atherosclerosis plaque formation was similar. However, the decrease of atherosclerosis in mice with combination of Ang-(1-7) and losartan was more remarkable relative to that of Ang-(1-7) or losartan alone. The decreases of macrophages infiltration, superoxide production and improvement of endothelium function in aortic lesions were more significant in combination group. In vitro study, we found that combination of Ang-(1-7) and losartan notably inhibited VSMCs proliferation and migration.
  
  
  CONCLUSIONS
  The anti-atherosclerosis effects of Ang-(1-7) and losartan in early lesion formation were equivalent. Combination use of both agents further enhanced the beneficial effects. Ang-(1-7) might add additional beneficial effect for patients with adequate ARB treatment.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Niu
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Guan
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China. Electronic address: zhangyun@sdu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China. Electronic address: zhangc@sdu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008055:Lipids / Q000097:blood; D019808:Losartan / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic; D012084:Renin-Angiotensin System / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D008055:Lipids; D010446:Peptide Fragments; D013481:Superoxides; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan
keywords: Angiotensin II type 1 receptor blocker; Angiotensin-(1–7); Atherosclerosis