Lactylation modification in cardio-cerebral diseases: A state-of-the-art review

Abstract

Cardio-cerebral diseases (CCDs), encompassing conditions such as coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, et al., represent a significant threat to human health and well-being. These diseases are often characterized by metabolic abnormalities and remodeling in the process of pathology. Glycolysis and hypoxia-induced lactate accumulation play critical roles in cellular energy dynamics and metabolic imbalances in CCDs. Lactylation, a post-translational modification driven by excessive lactate accumulation, occurs in both histone and non-histone proteins. It has been implicated in regulating protein function across various pathological processes in CCDs, including inflammation, angiogenesis, lipid metabolism dysregulation, and fibrosis. Targeting key proteins involved in lactylation, as well as the enzymes regulating this modification, holds promise as a therapeutic strategy to modulate disease progression by addressing these pathological mechanisms. This review provides a holistic picture of the types of lactylation and the associated modifying enzymes, highlights the roles of lactylation in different pathological processes, and synthesizes the latest clinical evidence and preclinical studies in a comprehensive view. We aim to emphasize the potential of lactylation as an innovative therapeutic target for preventing and treating CCD-related conditions.