Short-term vagus nerve stimulation reduces myocardial apoptosis by downregulating microRNA-205 in rats with chronic heart failure

Abstract

Previous studies have reported that short-term vagus nerve stimulation (VNS) improves cardiac function in rats with chronic heart failure (CHF). The molecular mechanisms are unclear. The potential effect of microRNA (miR)-205 in apoptosis of short-term VNS was examined. A total of 3 weeks after inducing CHF, the rats were divided into three groups: Sham stimulation in sham operated rats, sham stimulation in CHF rats (CHF-SS), and treated with VNS in CHF rats (CHF-VNS). The right vagus nerve of the neck was stimulated for 72 h in CHF rats with rectangular pulses of 40 msec duration at 1 Hz and 5 V. miR-205 was focused on, which exhibited differential expression in the miRNA microarray analysis of CHF rats, and the effects of VNS on apoptosis were examined. It was verified that the expression level of miR-205 in the CHF-SS group was increased, and the expression was reduced in the CHF-VNS group. Furthermore, mimics or inhibitor of miR-205 was transfected into H9c2 to investigate its function on apoptosis. Baculoviral IAP repeat-containing protein 2 (Birc2) was confirmed a target of miR-205 through a dual luciferase reporter assay and western blotting. It was demonstrated that downregulated miR-205 decreased apoptosis in H9c2 cells. The apoptosis-associated proteins were further detected in H9c2 cells and rat tissue. The mRNA and protein expression levels of caspase-3 and Bcl-2-associated X protein were decreased in the CHF-VNS group, the expression of Birc2 and B-cell lymphoma 2 were increased. The results were consistent with the in vitro study in the miR-205 inhibitor group. The present study demonstrated that short-term VNS decreased apoptosis by downregulating miR-205 in rats with CHF. Therefore, the results of the present study provide basic evidence for short-term VNS in the clinical treatment of CHF.

Inhibiting miR‐205 Alleviates Cardiac Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Function, and Apoptosis

“…Ling et al found that miR-205 was markedly inhibited in air pollution that induced myocardial inflammation, and the inhibition of miR-205 activated the IRAK2/TRAF6/NF- κ B signaling pathway [ 37 ]. Except these, miR-205 is also found to be increased in animals treated with imatinib mesylate and doxorubicin and animals with chronic heart failure [ 38 , 39 ]. We found that inhibiting miR-205 improved cardiac dysfunction and mitochondrial dysfunction and reduced infarct size, oxidative stress, and apoptosis by promoting Rnd3 in MI/R injury.…”

“…The cardiomyocyte apoptosis is the chief player in MI/R injury [ 48 ]. Previous studies have revealed that downregulating miR-205 reduces myocardial apoptosis in rats with chronic heart failure [ 39 ]. In the current study, miR-205 inhibitor inhibited, while miR-205 mimic promoted cardiomyocyte apoptosis.…”

Epigenetic regulation in myocardial infarction: Non-coding RNAs and exosomal non-coding RNAs

“…Treatment with imatinib mesylate and doxorubicin increased miR-205 expression in the plasma and heart of mice ( 89 ). Moreover, miR-205 downregulation significantly decreased myocardial apoptosis in rats with chronic heart failure ( 90 ). Cheng et al sought to understand how Remifentanil (a short-acting synthetic opioid analgesic drug) exerted its protective effects on myocardial I/R damage.…”

Effects of NRF-1 and PGC-1α cooperation on HIF-1α and rat cardiomyocyte apoptosis under hypoxia

“…It is the primary cause of cardiomyocyte injury [1,2]. Apoptosis is one of the primary forms of myocardial cell death [3,4], and hypoxia-induced apoptosis is a strong indicator of myocardial damage. We previously found that nuclear respiratory factor-1 (NRF-1) alleviates myocardial cell damage caused by cobalt chloride, an anoxic chemical agent, by inhibiting apoptosis [5].…”