RIPC improves myocardial injury by promoting mitochondrial protection via the PGC-1α/Nrf2 pathway.

Abstract

Myocardial infarction (MI) is a common condition with high morbidity and mortality rates. Remote ischemic preconditioning (RIPC) activates the endogenous protective mechanisms by promoting ischemic tolerance and mitigating the subsequent damage caused by fatal ischemia. Maintaining mitochondrial function is imperative for the prevention of myocardial ischemia. The current study aims to evaluate the therapeutic effects of RIPC on MI with a focus on the mechanisms involved in mitochondrial function. In our study, patients with MI who underwent coronary angiography were randomly assigned to either the RIPC group (n = 20) or the control group (n = 20). RIPC intervention was administered preoperatively by inflating a blood pressure cuff on the upper arm to 200 mmHg for four cycles of 5 min each, interspersed with 5-min reperfusion intervals. The process alleviated myocardial injury among the participants, accompanied by a significant elevation in the serum concentrations of PGC-1α and Nrf2 levels in the serum. In-vitro studies showed that RIPC can protect cardiomyocytes against ischemic injury by preserving the mitochondrial morphology, maintaining mitochondrial membrane integrity, and reducing oxidative stress. In-vivo experimental findings illustrated that RIPC mitigated myocardial structural damage in mice by augmenting mitochondrial function, leading to significant cardiac protection, as evidenced by improved cardiac function and reduced infarct size. Moreover, the protective effects of RIPC were abolished upon silencing of PGC-1α. Collectively, the results indicated that RIPC activates the PGC-1α/Nrf2 signaling pathway to rescue cardiomyocytes by maintaining mitochondrial function during ischemic insult, suggesting a promising strategy for preventing cardiac ischemia injury.