Abstract
In recent years, lactate has transitioned from being considered a mere metabolic end-product to being regarded as a critical signaling molecule that links cellular metabolism with gene regulation. Protein lactylation, a post-translational modification (PTM) mediated by lactate, is central to this functional transformation. In vascular diseases, the lactate-lactylation process demonstrates a marked double-edged sword characteristic, with its regulatory effects highly dependent on cell type, disease stage, and the pathological microenvironment. On one hand, lactylation can exert protective roles by promoting reparative gene expression, driving anti-inflammatory cell polarization, and maintaining myocardial structural integrity; on the other hand, aberrant lactylation can exacerbate inflammatory responses, promote fibrosis, and induce cell death and vascular calcification, thereby driving the development and progression of atherosclerosis, heart failure, and stroke. This review systematically delineates the paradoxical yet unified dual roles of lactylation across various vascular diseases and explores the molecular bases that underlie these functional differences. We propose that deciphering and precisely modulating the 'double-edged sword' of lactylation-selectively enhancing its protective functions while suppressing its pathological actions-represents a central challenge and a critical opportunity for translating basic research into clinical applications. Such advances could provide a novel theoretical framework for the development of diagnostic biomarkers and cell-specific precision therapeutic strategies.