Key result
Ivabradine pretreatment protected H9c2 cardiomyocytes against ischemia/reperfusion injury by reducing apoptosis and preserving mitochondrial function via the AMPK/SIRT1/PGC-1α signaling pathway.
Why the study?
Ivabradine shows protective effects against post-resuscitation myocardial dysfunction, but its underlying molecular mechanisms remain unknown.
Ivabradine protects cardiomyocytes against ischemia-reperfusion injury by improving mitochondrial energy metabolism and reducing oxidative stress via the AMPK/SIRT1/PGC-1α signaling pathway.
Hypothesis-generating in cell models; does not support clinical use of ivabradine for cardioprotection.
Post-resuscitation myocardial dysfunction (PRMD) is the most severe myocardial ischemia-reperfusion injury (MIRI) and is characterized by difficult treatment and poor prognosis. Research has shown the protective effects of the rational use of ivabradine (IVA) against PRMD; however, the molecular mechanisms of IVA remain unknown. In this study, an ischemia-reperfusion injury (IRI) model was established using hypoxic chambers. The results demonstrated that pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis. IVA attenuated mitochondrial damage, eliminated excess reactive oxygen species (ROS), suppressed IRI-induced ATP and NAD+ , and increased the AMP/ATP ratio. We further found that IVA increased the mRNA levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and upregulated the expression levels of phosphorylated AMP-activated protein kinase (p-AMPK)/AMPK, SIRT1, and PGC-1α proteins. Interestingly, no change in AMPK mRNA levels was observed. Cardiomyocyte energy metabolism significantly changed after IRI. The aim of this study was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway in myocardial ischemia/reperfusion injury-induced in H9c2 cell.
No takes yet. Share an insight, caveat, or question.
Zhu et al. (2020) studied Myocardial ischemia/reperfusion injury. Ivabradine vs. Ischemia-reperfusion injury without ivabradine was evaluated on Cell viability and apoptosis (p=<0.01). Ivabradine pretreatment protected H9c2 cardiomyocytes against ischemia/reperfusion injury by reducing apoptosis and preserving mitochondrial function via the AMPK/SIRT1/PGC-1α signaling pathway.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: