Effect of endostatin overexpression on angiotensin II-induced cardiac hypertrophy in rats
10.1097/CM9.0000000000000513
- Author:
You-Jin DAI
1
;
Jue-Xiao GONG
2
;
Rong BIAN
3
Author Information
1. Key Laboratory of Model Animal Research, Animal Core Facility of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu 210029, China
2. Department of Cardiology, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210014, China
3. Department of Rehabilitation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Publication Type:Journal Article
- Keywords:
Endostatin;
Cardiac hypertrophy;
Cardiomyocytes;
Cyclic adenosine monophosphate;
Protein kinase A
- From:
Chinese Medical Journal
2019;132(22):2716-2723
- CountryChina
- Language:English
-
Abstract:
Background:Endostatin, a biologically active fragment of collagen XVIII, has been observed in patients with ischemic heart disease. The aim of the present study was to investigate whether endostatin overexpression could attenuate cardiac hypertrophy by inhibiting the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling pathway.
Methods:This study was examined in vivo in rats and in vitro in primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Twenty-four male Sprague-Dawley rats were randomized into adenovirus (Ad)-green fluorescent protein, Ang II, Ad-endostatin, and Ang II + Ad-endostatin groups (n = 6 in each group). Four weeks later, all the rats were weighed and sacrificed after transthoracic echocardiography. Cardiac function was evaluated by transthoracic echocardiography, cardiomyocyte size was evaluated by hematoxylin-eosin staining. Levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were evaluated by quantitative reverse-transcription polymerase chain reaction or Western blotting, PKA level was evaluated by Western blotting, and cAMP level was evaluated by enzyme-linked immunosorbent assay. Statistical significance among multiple groups was evaluated by one-way analysis of variance.
Results:Endostatin overexpression reduced the increases in left ventricle (LV) mass (P = 0.0063), LV mass/body weight (BW) (P = 0.0013), interventricular septal thickness (IVS) in diastole (P = 0.0013), IVS in systole (P = 0.0056), left ventricular posterior wall thickness (LVPW) in diastole (P = 0.0291), LVPW in systole (P = 0.0080), heart weight (HW) (P = 0.0138), HW/BW (P = 0.0001), and HW/tibial length (P = 0.0372) in Ang II-treated rats. In addition, endostatin overexpression reduced cardiomyocyte cross-sectional area expansion, and reduced the levels of ANP and BNP in Ang II-treated rats (P = 0.0251 and 0.0477 for messenger RNA [mRNA]), and primary neonatal rat cardiomyocytes (P = 0.0188 and P = 0.0024 for mRNA; P = 0.0023 and 0.0013 for protein, respectively). Additionally, endostatin overexpression reduced the increase of cAMP (P = 0.0054) and PKA (P = 0.0328) levels in cardiomyocytes treated with Ang II. Treatment with cAMP reversed the effects of endostatin overexpression on ANP (P = 0.0263) and BNP (P = 0.0322) levels in cardiomyocytes induced by Ang II.
Conclusion:Endostatin overexpression could alleviate cardiac hypertrophy by inhibiting the cAMP-PKA signaling pathway.
