Role of protein lactylation in pulmonary and cardiovascular diseases: Current research and future perspectives (Review)

The cardiopulmonary system is highly coupled in structure and function. Metabolic and epigenetic disturbances constitute the common pathological basis for the progression of cardiopulmonary diseases and their comorbidities. Aberrant metabolic reprogramming triggers lactate accumulation. As a novel post-translational modification, protein lactylation participates in the regulation of inflammatory responses, cell death and fibrotic remodeling, thereby mediating cardiopulmonary dysfunction. Existing studies have separately illustrated the roles of lactylation in isolated pulmonary and cardiac disorders. Nevertheless, most investigations are confined to a single-organ perspective, lacking systematic summaries of common mechanisms for cardiopulmonary crosstalk and comorbidities. The present review summarized research advances of lactylation in various cardiopulmonary diseases, generalized its potential comorbid mechanisms, identified existing research gaps and translational obstacles for targeted therapy and collected lactylation-targeted intervention compounds with potential therapeutic effects reported in basic studies. The present review further outlined prospective research directions focused on spatiotemporal regulation of lactylation, metabolic-immune-epigenetic crosstalk that shapes disease progression, and the identification of specific targets in cardiopulmonary comorbidities, with the aim of providing a theoretical foundation for developing precise, broad-spectrum, co-targeted therapeutic strategies for cardiopulmonary diseases.