2022, Vol. 26 ›› Issue (20): 3184-3189

Effects of silent information regulator 1 on chronic heart failure in a postmenopausal mouse model and its mechanism

Zhang Haiyang1, Bi Shengli2, Feng Jingru1, Li Fan1, Wang Jing1, Zhao Na1, Li Xinjun1   

Abstract: BACKGROUND: Decreased serum estradiol in postmenopausal women with coronary heart disease is related to decreased heart function and ventricular remodeling aggravation. The effect of menopause on chronic heart failure and its mechanism are still unclear. Silent information regulator 1 plays a protective role in the cardiovascular system.
OBJECTIVE: To investigate the effect of silent information regulator 1 on aggravating chronic heart failure in ovariectomized mice and its mechanism.
METHODS: Experiment 1: Wild-type female C57BL/6J mice and female C57BL/6J mice with knockout of silent information regulator 1 were selected. The wild-type mice were randomly divided into four groups: a sham surgery group, an aortic stenosis group, an ovariectomy+aortic stenosis group, and an ovariectomy+aortic stenosis+estradiol group. From the first day after surgery, mice in the ovariectomy+aortic stenosis+estradiol group were given subcutaneous injection of estradiol benzoate at a dose of 0.2 mg/kg per day, and mice in the other groups were injected subcutaneously with the same dose of normal saline for 8 weeks. Experimental 2: Mice with knockout of silent information regulator 1 were randomly divided into a silent information regulator 1 knockout+sham surgery group and a silent information regulator 1 knockout+aortic stenosis group. Experimental 3: There were five experimental groups: a negative control adenovirus group, a negative control adenovirus+aortic stenosis group, an overexpression of silent information regulator 1 adenovirus+aortic stenosis group, a negative control+adenovirus ovariectomy+aortic stenosis group, and an adenovirus overexpressing silent information regulator 1+ovariectomy+aortic stenosis group. Overexpression of silent information regulator 1 was achieved by multi-point injection of negative control adenovirus or adenovirus overexpressing silent information regulator 1. Eight weeks after modeling, we detected the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, serum estradiol level, brain natriuretic peptide level, uterine mass, myocardial pathological changes, and the expression level of silent information regulator 1.
RESULTS AND CONCLUSION: Compared with the sham surgery group, the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and serum brain natriuretic peptide level were significantly increased, and the left ventricular ejection fraction and the expression level of myocardial silent information regulator 1 were significantly decreased in the aortic stenosis group (P < 0.05). Compared with the aortic coarctation group, the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and serum brain natriuretic peptide level were significantly increased, and the left ventricular ejection fraction, serum estradiol level, and the expression level of myocardial silent information regulator 1 were significantly reduced in the ovariectomized+aortic stenosis group (P < 0.05). Compared with the aortic coarctation group, silent information regulator 1 was not expressed in the silent information regulator 1 knockout+aortic stenosis group, in which the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and serum brain natriuretic peptide level were significantly increased, and the left ventricular ejection fraction was significantly decreased (P < 0.05). Compared with the negative control adenovirus+ovariectomy+aortic stenosis group, the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and serum brain natriuretic peptide level were significantly reduced, and the left ventricular ejection fraction and the expression level of myocardial silent information regulator 1 were significantly increased in the adenovirus overexpressing silent information regulator 1+ovariectomy+aortic stenosis group (P < 0.05). These results indicate that ovariectomy can aggravate chronic heart failure in mice, and the molecular mechanism is to inhibit the expression of silent information regulator 1 in myocardium.
Key words: menopause, ovariectomy, chronic heart failure, silent information regulator 1, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, brain natriuretic peptide