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. METHODS AND 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.
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. METHODS AND 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.
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Authors: Sean E Thatcher; Xuan Zhang; Deborah A Howatt; Hong Lu; Susan B Gurley; Alan Daugherty; Lisa A Cassis Journal: Arterioscler Thromb Vasc Biol Date: 2011-01-20 Impact factor: 8.311
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Authors: Rodrigo A Fraga-Silva; Fabiana P Costa-Fraga; Tatiane M Murça; Patrícia L Moraes; Augusto Martins Lima; Roberto Q Lautner; Carlos H Castro; Célia Maria A Soares; Clayton L Borges; Ana Paula Nadu; Marilene L Oliveira; Vinayak Shenoy; Michael J Katovich; Robson A S Santos; Mohan K Raizada; Anderson J Ferreira Journal: Hypertension Date: 2013-04-22 Impact factor: 10.190
Authors: Rodrigo A Fraga-Silva; Fabrizio Montecucco; Fabiana P Costa-Fraga; Alessio Nencioni; Irene Caffa; Maiia E Bragina; François Mach; Mohan K Raizada; Robson A S Santos; Rafaela F da Silva; Nikolaos Stergiopulos Journal: Vascul Pharmacol Date: 2015-08-22 Impact factor: 5.773