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
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