Knockdown of Salusin-β Improves Cardiovascular Function in Myocardial Infarction-Induced Chronic Heart Failure Rats.

Yu Xu,Ying Han,Aidong Chen,Xuanxuan Liu,Xinyu Tang,Yan Pan,Xingxing Wang,Qingping Feng

doi:10.1155/2021/8896226

Yu Xu, Ying Han + Show 6 more

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https://doi.org/10.1155/2021/8896226

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Abstract

Salusin-β is a biologically active peptide with 20 amino acids that exerts several cardiovascular activity-regulating effects, such as regulating vascular endothelial function and the proliferation of vascular smooth muscle cells. However, the regulatory effects of salusin-β in myocardial infarction-induced chronic heart failure (CHF) are still unknown. The current study is aimed at investigating the effects of silencing salusin-β on endothelial function, cardiac function, vascular and myocardial remodeling, and its underlying signaling pathways in CHF rats induced by coronary artery ligation. CHF and sham-operated (Sham) rats were subjected to tail vein injection of adenoviral vectors encoding salusin-β shRNA or a control-shRNA. The coronary artery (CA), pulmonary artery (PA), and mesenteric artery (MA) were isolated from rats, and isometric tension measurements of arteries were performed. Compared with Sham rats, the plasma salusin-β, leptin and visfatin levels and the salusin-β protein expression levels of CA, PA, and MA were increased, while the acetylcholine- (ACh-) induced endothelium-dependent vascular relaxation of CA, PA, and MA was attenuated significantly in CHF rats and was improved significantly by salusin-β gene knockdown. Salusin-β knockdown also improved cardiac function and vascular and myocardial remodeling, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels, and decreased NAD(P)H oxidase activity, NOX-2 and NOX-4 expression, and reactive oxygen species (ROS) levels in arteries in CHF rats. The effects of salusin-β knockdown in CHF rats were attenuated significantly by pretreatment with the NOS inhibitor L-NAME. These results indicate that silencing salusin-β contributes to the improvement of endothelial function, cardiac function, and cardiovascular remodeling in CHF by inhibiting NAD(P)H oxidase-ROS generation and activating eNOS-NO production.

Highlights

Chronic heart failure (CHF) is the terminal stage of a variety of cardiovascular diseases and is characterized by progressive left ventricular dysfunction and declining ejection fraction (EF), usually accompanied by vascular endothelial dysfunction, neuroendocrine activation, and ventricular remodeling [1,2,3]
The body weight (BW) was not significantly different between CHF and Sham rats, the heart weight (HW) and the HW/BW were increased in CHF rats, which suggested the occurrence of myocardial hypertrophy
Compared with the Sham rats, the systolic arterial pressure (SAP), pulse pressure (PP), LV peak systolic pressure (LVSP), LV developed pressure (LVDP), and Left Ventricular (LV) +dP/dtmax decreased, while left ventricular enddiastolic pressure (LVEDP) increased significantly in CHF rats, which was consistent with our previous study findings [46]

Summary

Introduction

Chronic heart failure (CHF) is the terminal stage of a variety of cardiovascular diseases and is characterized by progressive left ventricular dysfunction and declining ejection fraction (EF), usually accompanied by vascular endothelial dysfunction, neuroendocrine activation, and ventricular remodeling [1,2,3]. Vascular endothelial dysfunction usually occurs at the early stages of heart failure and is closely related to the development of CHF and is a predictor of adverse events, such as cardiovascular remodeling in CHF patients [4, 5]. Vascular endothelial cells (VECs) can release vasoconstrictor factors, such as endothelin-1, and vasodilatation factors, such as nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostaglandin (PGI2), to control vascular tone. The release of vasoconstrictor factors and vasodilatation factors from VECs becomes imbalanced.

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