Targeting Ferroptosis-Inflammation Crosstalk: A Novel Strategy for the Prevention and Treatment of Myocardial Ischaemia Reperfusion Injury

Myocardial ischaemia-reperfusion injury (MIRI) is a major cause of residual myocardial damage following coronary revascularisation. Unfortunately, effective mechanism-based pharmacological interventions that can be translated into clinical practice remain limited. Emerging evidence indicates that ferroptosis and inflammation mutually reinforce each other and constitute a critical pathological process responsible for the amplification of myocardial injury during the early phase of reperfusion. Upon myocardial reperfusion, ferroptotic cardiomyocytes release damage-associated molecular patterns and disrupt tissue barriers, thereby activating the innate immune system and initiating inflammatory responses. In turn, inflammation promotes oxidative stress, dysregulation of iron metabolism and lipid peroxidation through the activation of inflammatory signaling pathways and the release of pro-inflammatory mediators, ultimately exacerbating ferroptosis. This reciprocal interaction establishes a self-perpetuating vicious cycle that contributes to the progression of MIRI. Encouragingly, several Western medicines and bioactive compounds derived from traditional Chinese medicine have shown therapeutic potential in modulating MIRI. This review systematically summarizes the molecular mechanisms underlying the bidirectional interaction between ferroptosis and inflammation in MIRI and discusses emerging pharmacological strategies targeting this pathological network. Collectively, the available evidence suggests that future therapeutic approaches to MIRI should extend beyond reperfusion therapy, antioxidant treatment, or anti-inflammatory intervention alone and instead consider combined strategies that simultaneously suppress inflammation and ferroptosis. Such an integrated approach may provide a novel translational framework for early risk assessment, therapeutic response prediction and targeted intervention in patients with MIRI.