title: Endogenous activated angiotensin-(1-7) plays a protective effect against atherosclerotic plaques unstability in high fat diet fed ApoE knockout mice.
abstract: OBJECTIVE
  We recently found that exogenous angiotensin-(1-7) [Ang-(1-7)] inhibits Angiotensin II (Ang-II)-induced atherosclerotic lesion formation and enhances plaque stability. Our objective was to evaluate the role of endogenous activated Ang-(1-7) during atherosclerosis.
  
  
  RESULTS
  In mice, the effects of endogenous Ang-(1-7) on atherogenesis in early stage and plaque stability in late stage were observed in ApoE knockout (ApoE-/-) mice fed with a high fat diet. Blockage of endogenous Ang-(1-7) with A779, an Ang-(1-7) antagonist, did not increase early plaque lesion formation, however, it remarkably enhanced contents of lipids and macrophages and decreased contents of vascular smooth muscle cells (VSMCs) and collagens in late lesions. The expressions of proinflammatory cytokines, and the expressions and activities of matrix metalloproteinases were significantly elevated in A779-treated group than those in vehicle-treated group in late lesions. Exogenous Ang-(1-7) treatment attenuated early atherosclerotic plaque formation and enhanced late plaques stability in this model. The contents of Ang-II and Ang-(1-7) and activity of ACE2 in late atherosclerotic plaques were higher than those of early atherosclerotic lesions.
  
  
  CONCLUSIONS
  Endogenous activated Ang-(1-7) enhanced late atherosclerotic plaques stability but did not affect early atherosclerotic plaque formation. Therapies to elevate endogenous Ang-(1-7) may be a potentially effective approach to attenuate atherosclerotic plaques vulnerability.
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: 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: 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: Tao
authors.initials: T
authors.lastname: Guo
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: Jing
authors.initials: J
authors.lastname: Kong
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: Kai
authors.initials: K
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: 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 / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D059305:Diet, High-Fat / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D001057:Apolipoproteins E; D018836:Inflammation Mediators; D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Angiotensin-(1-7); Atherosclerosis; Plaque stability; Renin–angiotensin system