Protein lactylation in myocardial ischemia-reperfusion injury: mechanisms and therapeutic potential

Myocardial ischemia-reperfusion injury (MIRI) remains a major unresolved problem in cardiovascular medicine. It commonly occurs in coronary heart disease (CHD) patients following reperfusion therapy or cardiopulmonary bypass (CPB)-assisted cardiac surgery. Despite the clinical necessity of restoring blood flow, reperfusion itself paradoxically exacerbates myocardial injury. The resulting therapeutic dilemma underscores the need for innovative cardioprotective strategies. Recent studies suggest that protein lactylation (Kla), a newly identified post-translational modification (PTM) derived from lactate metabolism, plays a crucial role in cardiomyocytes by regulating metabolic adaptation, injury repair, stress responses, cell death, and cardiac remodeling. However, there is still no comprehensive synthesis of the role of Kla in MIRI. In this review, we critically examine the emerging evidence linking Kla to the pathogenesis of MIRI and further discuss potential therapeutic strategies targeting this epigenetic mechanism to alleviate reperfusion-induced myocardial injury.