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

doi:10.12307/2022.618

Abstract

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

CLC Number:

Zhang Haiyang, Bi Shengli, Feng Jingru, Li Fan, Wang Jing, Zhao Na, Li Xinjun. Effects of silent information regulator 1 on chronic heart failure in a postmenopausal mouse model and its mechanism[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(20): 3184-3189.

Figures/Tables 10

References

[1] FREANEY PM, KHAN SS, LLOYD-JONES DM, et al. The Role of Sex-Specific Risk Factors in the Risk Assessment of Atherosclerotic Cardiovascular Disease for Primary Prevention in Women. Curr Atheroscler Rep. 2020;22(9):46.
[2] ZHU D, CHUNG HF, DOBSON AJ, et al. Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies. Hum Reprod. 2020;35(8):1933-1943.
[3] 汤展, 马懿, 钟元林, 等. 绝经后冠心病患者血浆雌二醇与心室重构及NT-proBNP的相关性[J]. 中国老年学杂志,2015,35(9):2381-2383.
[4] 拓步雄, 徐杰, 邹倩, 等. 慢性心力衰竭血清Hcy、MIP-1α、SIRT1水平检测的价值研究[J]. 解放军医药杂志,2020,32(10):36-39,44.
[5] SASAKI Y, IKEDA Y, MIYAUCHI T, et al. Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis. J Atheroscler Thromb. 2020;27(1):47-59.
[6] GUO JM, SHU H, WANG L, et al. SIRT1-dependent AMPK pathway in the protection of estrogen against ischemic brain injury. CNS Neurosci Ther. 2017;23(4):360-369.
[7] 雷迁, 魏新川, 徐金东, 等. 超声评价微创横向主动脉缩窄小鼠模型心脏重构变化[J]. 西部医学,2019,31(4):503-507.
[8] CHEN H, LIU S, ZHAO C, et al. Cardiac contractility modulation improves left ventricular systolic function partially via miR-25 mediated SERCA2A expression in rabbit trans aortic stenosis heart failure model. J Thorac Dis. 2018;10(6):3899-3908.
[9] AHMAD F, SINGH AP, TOMAR D, et al. Cardiomyocyte-GSK-3alpha promotes mPTP opening and heart failure in mice with chronic pressure overload. J Mol Cell Cardiol. 2019;130:65-75.
[10] LOPES ACR, ZAVAN B, CORRÊA YJC, et al. Impact of obesity and ovariectomy on respiratory function in female mice. Respir Physiol Neurobiol. 2021; 17(294):103775.
[11] Wang X, Lu L, Tan Y, et al. GPR 30 reduces myocardial infarct area and fibrosis in female ovariectomized mice by activating the PI3K/AKT pathway. Life Sci. 2019;1(226):22-32.
[12] CAMARGO TF, ZANESCO AM, PACHER KAS, et al. Physiological profile regulation during weight gain and loss by ovariectomized females: importance of SIRT1 and SIRT4. Am J Physiol Endocrinol Metab. 2020; 319(4):E769-E778.
[13] JIANG Y, LUO W, WANG B, et al. Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice. Life Sci. 2020;1(246): 117422.
[14] NIE Q, ZHANG J, HE B, et al. A novel mechanism of protection against isoproterenol-induced cardiac inflammation via regulation of the SIRT1/NRF2 signaling pathway with a natural SIRT1 agonist. Eur J Pharmacol. 2020;5(886):173398.
[15] HWANG DK, CHANG YL, LIN TC, et al. Changes in the Systemic Expression of Sirtuin-1 and Oxidative Stress after Intravitreal Anti-Vascular Endothelial Growth Factor in Patients with Retinal Vein Occlusion. Biomolecules. 2020; 10(10):1414.
[16] LI B, LI M, LI X, et al. Sirt1-inducible deacetylation of p21 promotes cardiomyocyte proliferation. Aging (Albany NY). 2019;11(24):12546-12567.
[17] LIN B, ZHAO H,LI L,et al. Sirt1 improves heart failure through modulating the NF-kappaB p65/microRNA-155/BNDF signaling cascade. Aging (Albany NY). 2020;18:12.
[18] VÁZQUEZ-GARZA E, BERNAL-RAMÍREZ J, JERJES-SÁNCHEZ C, et al. Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature. Oxid Med Cell Longev. 2020;3(2020):1841527.