Combination of angiotensin-(1-7) with perindopril is better than single therapy in ameliorating diabetic cardiomyopathy.
We recently found that overexpression of angiotensin (Ang)-converting enzyme 2, which metabolizes Ang-II to Ang-(1-7) and Ang-I to Ang-(1-9), may improve left ventricular remodeling in diabetic cardiomyopathy. Here we aimed to test whether chronic infusion of Ang-(1-7) can dose-dependently ameliorate left ventricular remodeling and function in a rat model of diabetic cardiomyopathy and whether the combination of Ang-(1-7) and Ang-converting enzyme inhibition may be superior to single therapy. Our results showed that Ang-(1-7) treatment dose-dependently ameliorated left ventricular remodeling and dysfunction in diabetic rats by attenuating myocardial fibrosis, myocardial hypertrophy and myocyte apoptosis via both the Mas receptor and angiotensin II type 2 receptor. Furthermore, combining Ang-(1-7) with perindopril provided additional cardioprotection relative to single therapy. Ang-(1-7) administration provides a novel and promising approach for treatment of diabetic cardiomyopathy.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Panpan
P
Hao
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Jianmin
J
Yang
Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-cerebral Vascular Diseases, Shandong Medical Imaging Research Institute, Shandong University, Jinan 250021, Shandong, China.
Yanping
Y
Liu
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Mingxiang
M
Zhang
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Kai
K
Zhang
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Fei
F
Gao
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Yuguo
Y
Chen
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Cheng
C
Zhang
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
Yun
Y
Zhang
D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D058065:Diabetic Cardiomyopathies / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000517:prevention & control; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001786:Blood Glucose; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D053773:Transforming Growth Factor beta1; D003094:Collagen; D000803:Angiotensin I; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D020913:Perindopril