title: ACE2 and Ang-(1-7) protect endothelial cell function and prevent early atherosclerosis by inhibiting inflammatory response.
abstract: BACKGROUND
  Angiotensin-converting enzyme 2 (ACE2) is a counter-regulator against ACE by converting angiotensin II (Ang-II) to Ang-(1-7), but the effect of ACE2 and Ang-(1-7) on endothelial cell function and atherosclerotic evolution is unknown. We hypothesized that ACE2 overexpression and Ang-(1-7) may protect endothelial cell function by counterregulation of angiotensin II signaling and inhibition of inflammatory response.
  
  
  METHODS
  We used a recombinant adenovirus vector to locally overexpress ACE2 gene (Ad-ACE2) in human endothelial cells in vitro and in apoE-deficient mice in vivo. The Ang II-induced MCP-1, VCAM-1 and E-selectin expression, endothelial cell migration and adhesion of human monocytic cells (U-937) to HUVECs by ACE2 gene transfer were evaluated in vitro. Accelerated atherosclerosis was studied in vivo, and atherosclerosis was induced in apoE-deficient mice which were divided randomly into four groups that received respectively a ACE2 gene transfer, Ad-ACE2, Ad-EGFP, Ad-ACE2 + A779, an Ang-(1-7) receptor antagonist, control group. After a gene transfer for 4 weeks, atherosclerotic pathology was evaluated.
  
  
  RESULTS
  ACE2 gene transfer not only promoted HUVECs migration, inhibited adhesion of monocyte to HUVECs and decreased Ang II-induced MCP-1, VCAM-1 and E-selectin protein production in vitro, but also decreased the level of MCP-1, VCAM-1 and interleukin 6 and inhibit atherosclerotic plaque evolution in vivo. Further, administration of A779 increased the level of MCP-1, VCAM-1 and interleukin 6 in vivo and led to further advancements in atherosclerotic extent.
  
  
  CONCLUSIONS
  ACE2 and Ang-(1-7) significantly inhibit early atherosclerotic lesion formation via protection of endothelial function and inhibition of inflammatory response.
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yue-Hui
authors.initials: YH
authors.lastname: Zhang
authors.forename: Yong-huan
authors.initials: YH
authors.lastname: Zhang
authors.forename: Xue-Fei
authors.initials: XF
authors.lastname: Dong
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Hao
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhou
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Yu
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Abdulai Fallah
authors.initials: AF
authors.lastname: Tengbeh
authors.forename: Bo
authors.initials: B
authors.lastname: Dong
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000502:physiology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D018014:Gene Transfer Techniques; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; C111835:CCL2 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019040:E-Selectin; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)