title: Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis.
abstract: OBJECTIVE
  The purpose of this study was to test the hypothesis that ACE2 overexpression may enhance atherosclerotic plaque stability by antagonizing ACE activity and converting angiotensin II to angiotensin 1-7.
  
  
  RESULTS
  Atherosclerotic plaques were induced in the abdominal aorta of 114 rabbits by endothelial injury and atherogenic diet. Gene therapy was performed in group A at week 4 and in group B at week 12, respectively. Each group of rabbits were randomly divided into 3 subgroups which received, respectively, a recombinant ACE2 expressing vector (AdACE2), a control vector AdEGFP and AdACE2+A779, an antagonist of angiotensin 1-7 receptor. Local ACE2 overexpression attenuated the progression of lesions from week 4 to week 8, but not progression of plaque size from week 12 to week 16. In group B rabbits, local ACE2 overexpression resulted in stable plaque compositions, ie, fewer macrophages, less lipid deposition and more collagen contents, higher plaque stability scores, decreased angiotensin II levels, and increased angiotensin 1-7 levels in plaque tissues in the AdACE2 subgroup compared with those in the AdEGFP subgroup.
  
  
  CONCLUSIONS
  Overexpression of ACE2 results in stabilized atherosclerotic plaques and the mechanism is probably the conversion of vasoconstrictive angiotensin II to vessel protective angiotensin 1-7.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dong
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Jing Bo
authors.initials: JB
authors.lastname: Feng
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Zhao
authors.forename: Shu Ying
authors.initials: SY
authors.lastname: Li
authors.forename: Ya Pei
authors.initials: YP
authors.lastname: Yang
authors.forename: Qiu Li
authors.initials: QL
authors.lastname: Dong
authors.forename: Bi Ping
authors.initials: BP
authors.lastname: Deng
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Qing Tao
authors.initials: QT
authors.lastname: Yu
authors.forename: Chun Xi
authors.initials: CX
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Chun Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Huai Dong
authors.initials: HD
authors.lastname: Song
authors.forename: Ming Xiang
authors.initials: MX
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D050197:Atherosclerosis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: C092006:7-Ala-angiotensin (1-7); D004041:Dietary Fats; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D003094:Collagen; 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)