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

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.

Upregulated expression of a TOR2A gene product‐salusin‐β in the paraventricular nucleus enhances sympathetic activity and cardiac sympathetic afferent reflex in rats with chronic heart failure induced by coronary artery ligation

“…In addition, the plasma level of salusin-β in coronary artery ligation-induced CHF rats is much higher than that in Sham rats. 24 The salusin-β expression in the PVN of aged spontaneously hypertensive rat with heart failure is remarkably elevated compared with that in control rats. 36 Microinjection of salusin-β into the PVN or RVLM, two important central nuclei controlling sympathetic outflow, increases blood pressure and sympathetic nerve activity and contributes to the exaggerated sympatho-excitation in hypertensive rats.…”

“…[21][22][23] Inhibition of salusin-β expression in the peripheral circulation promotes cardiac function and ameliorates cardiovascular remodeling by improving endothelial function and vasodilation in CHF rats. 24 However, whether salusin-β in the central nervous system of myocardial infarction-induced CHF plays an important role in enhancing the CSAR and overexciting sympathetic activity and eventually decreases cardiac function remains unclear.…”

“…[21][22][23] Silencing salusin-β in the peripheral circulation improves endothelial function, cardiovascular remodeling, and cardiac function in CHF. 24 However, whether salusin-β in the PVN regulates enhanced CSAR and sympathetic hyperactivation and eventually affects cardiac function in CHF induced by coronary artery ligation remains unclear.…”

Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells

“…Knockdown with salusin- β shRNA in the coronary, pulmonary, and mesenteric arteries of a rat model of chronic heart failure improved cardiac function and vascular remodeling [ 147 ].…”

Advances in the study of nicotinamide adenine dinucleotide phosphate oxidase in myocardial remodeling

“…However, NOX2 is deleterious in oxidative stress, and salusin-β is a bioactive peptide with 20 amino acids that can regulate the proliferative activity of vascular endothelial and smooth muscle cells. Salusin-β inhibits NOX-mediated ROS production, activates eNOS and NO production, causes dysregulation of the balance of contractile and vasodilator factors released from the vascular endothelium ( 101 ), improves endothelial dysfunction, cardiovascular remodeling, and cardiac dysfunction, and promotes early depolarization of rabbit cardiomyocytes by activating the calmodulin-dependent protein kinase II (CaMKII) pathway. Studies demonstrated its use as a downstream target of NOX2 to increase the incidence of arrhythmias in AngII-induced mouse models ( 102 , 103 ), suggesting that NOX2 is involved in cardiac structural remodeling.…”