title: ACE2 overexpression inhibits angiotensin II-induced monocyte chemoattractant protein-1 expression in macrophages.
abstract: BACKGROUND
  The discovery of angiotensin-converting enzyme 2 (ACE2) has shed light on the potential therapy for cardiovascular disease, owing to its key role in the formation of vasoprotective peptide angiotensin (Ang 1-7) from angiotensin (Ang) II. The aim of this study was to evaluate whether ACE2 overexpression could protect human monocyte cell line (THP-1) macrophages from angiotensin II-induced monocyte chemoattractant protein-1 (MCP-1) formation.
  
  
  METHODS
  A truncated form of mouse ACE2 (mACE2) was cloned into adenovirus vector (Ad-ACE2) and transfected into THP-1. We examined expression of MCP-1 by administration of a selected Ang (1-7) antagonist (A779) to show the effect of ACE2 overexpression on MCP-1 level induced by AngII.
  
  
  RESULTS
  AngII-induced MCP-1 expression increased obviously at 24 h and at the concentration of 10(-6) M. Transduction of THP-1 with Ad-ACE2 resulted in a viral increase in ACE2 activity. This was associated with a significant attenuation of AngII-induced MCP-1 production by 39.6+/-4.0% in THP-1 (mean+/-SEM, n=3). Moreover, expression of MCP-1 increased by 35.1+/-4.2% in Ad-ACE2 transfected THP-1 after incubation with Ang II and A779 compared to that with AngII alone. Collectively, these results indicated that ACE2 overexpression in the THP-1 attenuates AngII-induced MCP-1 production and that this reduction is likely mediated by increased Ang (1-7) level.
  
  
  CONCLUSIONS
  ACE2 overexpression may provide a new therapeutic strategy for atherosclerosis by inhibiting MCP-1 production induced by AngII.
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, PR China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Guo
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.forename: Lian-Qun
authors.initials: LQ
authors.lastname: Cui
mesh_terms: D000803:Angiotensin I; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D010446:Peptide Fragments; 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)