Inhibitor of growth protein-2 silencing alleviates angiotensin Ⅱ-induced cardiac remodeling in mice by reducing p53 acetylation.
10.12122/j.issn.1673-4254.2023.07.09
- Author:
Zhengwang LIU
1
;
Xiaotang QIU
2
;
Hua YANG
1
;
Xiaocui WU
2
;
Wenjing YE
3
Author Information
1. Department of Cardiovascular Medicine, Chinese Traditional Medicine Hospital of Hainan Province, Haikou 570203, China.
2. Department of Endocrinology, Chinese Traditional Medicine Hospital of Hainan Province, Haikou 570203, China.
3. Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
- Publication Type:Journal Article
- Keywords:
P53;
angiotensinⅡ;
cardiac remodeling;
inhibitor of growth protein-2;
myocardial hypertrophy
- MeSH:
Animals;
Mice;
Angiotensin II;
Tumor Suppressor Protein p53;
Acetylation;
Stroke Volume;
Ventricular Remodeling;
Ventricular Function, Left;
Myocytes, Cardiac
- From:
Journal of Southern Medical University
2023;43(7):1127-1135
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism.
METHODS:An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg-1 · min-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits.
RESULTS:The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression.
CONCLUSION:Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.
