Angiotensin-Converting Enzyme-2 Overexpression Improves Left Ventricular Remodeling and Function in a Rat Model of Diabetic Cardiomyopathy
Autor: | Zhao Li Zhou, Fei Gao, Yun Zhang, Chun Ming Pan, Cheng Zhang, Lei Zhang, Shu Ying Li, Nan Wang, Bo Dong, Hong Jiang, Qing Tao Yu, Yue Hui Zhang, Huai Dong Song, Yan Yan Gao, Hui Xu, Hong Jun Bian, Hong Yan Dai, Chun Xi Liu |
---|---|
Jazyk: | angličtina |
Předmět: |
Male
medicine.medical_specialty Diabetic Cardiomyopathies Heart Ventricles Blotting Western heart failure Peptidyl-Dipeptidase A angiotensin II Real-Time Polymerase Chain Reaction Ventricular Function Left Diabetes Mellitus Experimental angiotensin-converting enzyme 2 Internal medicine Diabetic cardiomyopathy medicine diabetic cardiomyopathy Animals RNA Messenger Rats Wistar Ventricular remodeling Fibroblast Ventricular Remodeling business.industry Myocardium medicine.disease Streptozotocin Angiotensin II Immunohistochemistry gene therapy Rats Endocrinology medicine.anatomical_structure Losartan Gene Expression Regulation Echocardiography Angiotensin-converting enzyme 2 Myocardial fibrosis business Cardiology and Cardiovascular Medicine hormones hormone substitutes and hormone antagonists medicine.drug |
Zdroj: | Journal of the American College of Cardiology. (8):739-747 |
ISSN: | 0735-1097 |
DOI: | 10.1016/j.jacc.2011.09.071 |
Popis: | Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular (LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy. |
Databáze: | OpenAIRE |
Externí odkaz: |