Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis.
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.
Dong
Bo
B
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.
Zhang
Cheng
C
Feng
Jing Bo
JB
Zhao
Yu Xia
YX
Li
Shu Ying
SY
Yang
Ya Pei
YP
Dong
Qiu Li
QL
Deng
Bi Ping
BP
Zhu
Li
L
Yu
Qing Tao
QT
Liu
Chun Xi
CX
Liu
Bin
B
Pan
Chun Ming
CM
Song
Huai Dong
HD
Zhang
Ming Xiang
MX
Zhang
Yun
Y
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
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)