摘要
Abstract
Vascular malformations are a group of congenital disorders caused by abnormal vascular development,with complex clinical phenotypes,slow progression,and a lack of effective molecularly targeted therapies.In recent years,with the in-depth research on the intersection of metabolic reprogramming and epigenetic regulation,a novel form of epigenetic modification,lysine lactylation(Kla),has attracted widespread attention for its potential role in regulating gene expression and cell fate.However,the role of Kla in the pathogenesis of Vascular malformations has not been systematically explored.This paper focuses on the regulatory mechanism of Kla and the biological function of Kla,and systematically sort out the role of Kla in the regulation of angiogenesis and functional remodeling of endothelial cells,taking into account the recent domestic and international research advances in histone lactylation,endothelial cell metabolism shaping,and vascular developmental abnormalities.Then this paper further proposes that the pathological basis of PIK3CA mutation,enhanced glycolysis and microenvironmental hypoxia,which are common in vascular malformations,may be involved in lesion development by inducing lactate accumulation and Kla upregulation,which affects transcriptional regulation and endothelial behavior.Finally,this paper combines the existing data to deduce the possible regulatory mechanism of Kla in vascular malformations,and suggests that in the future,the role and application prospect of Kla in vascular malformations should be deeply explored from the directions of spatial genomics,metabolome-epigenome joint analysis,and in vivo functional validation model construction.This review is expected to provide a new perspective for exploring the function of metabolic-epigenetic regulatory axis in vascular developmental abnormalities,and provide a theoretical basis for molecular mechanism studies and development of targeted therapeutic strategies for vascular malformations.关键词
脉管畸形/乳酸化修饰/发病机制/PIK3CA突变/表观遗传修饰Key words
Vascular malformations/Lysine lactylation/Pathogenesis/PIK3CA mutation/Epigenetic modification分类
医药卫生
