title: Angiotensin-(1-7) dose-dependently inhibits atherosclerotic lesion formation and enhances plaque stability by targeting vascular cells.
abstract: OBJECTIVE
  To test the hypothesis that chronic infusion of angiotensin-(1-7) [Ang-(1-7)] may dose-dependently inhibit atherosclerotic lesion formation by targeting vascular smooth muscle cells and a large dose of Ang-(1-7) may stabilize mature plaque by targeting macrophages.
  
  
  RESULTS
  In vivo, the effects of Ang-(1-7) on atherogenesis and plaque stability were observed in ApoE(-/-) mice fed a high-fat diet and chronic angiotensin II infusion. In vitro, the effects of Ang-(1-7) on vascular smooth muscle cells' proliferation and migration, and macrophage inflammatory cytokines were examined. Ang-(1-7) dose-dependently attenuated early atherosclerotic lesions and inhibited vascular smooth muscle cells' proliferation and migration via suppressing extracellular regulated protein kinase/P38 mitogen-activated protein kinase and janus kinase/signal transducers and activators of transcription activities and enhancing smooth muscle 22α and angiotensin II type 2 receptor expression. Ang-(1-7) treatment resulted in high contents of collagen and vascular smooth muscle cells, and low contents of macrophages and lipids in carotid mature plaques. Ang-(1-7) lowered the expression levels of proinflammatory cytokines and activities of matrix metalloproteinases in mature plaques.
  
  
  CONCLUSIONS
  Ang-(1-7) treatment inhibits early atherosclerotic lesions and increases plaque stability in ApoE(-/-) mice, thus providing a novel and promising approach to the treatment of atherosclerosis.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Jian Min
authors.initials: JM
authors.lastname: Yang
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Xiao
authors.initials: X
authors.lastname: Meng
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Zhao
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Yang
authors.forename: Xiao Ling
authors.initials: XL
authors.lastname: Liu
authors.forename: Pan Pan
authors.initials: PP
authors.lastname: Hao
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Xu Ping
authors.initials: XP
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Xue Qiang
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Ming Xiang
authors.initials: MX
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D008840:Microfilament Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; C058992:Tagln protein, mouse; D014665:Vasodilator Agents; D003094:Collagen; D000803:Angiotensin I; D020782:Matrix Metalloproteinases; C118790:angiotensin I (1-7)
keywords: angiotensin II; angiotensin-(1–7); atherosclerosis; plaque, atherosclerotic