组织工程与重建外科杂志

组织工程与重建外科杂志 ›› 2026, Vol. 22 ›› Issue (1): 95-.

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乳酸化修饰在脉管畸形中的研究进展与机制探讨

  

  • 出版日期:2026-01-29 发布日期:2026-03-06

Progress and mechanism of lysine lactylation in vascular malformations

  • Online:2026-01-29 Published:2026-03-06

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摘要：

脉管畸形是一类由血管发育异常引起的先天性疾病，其临床表型复杂，病情进展缓慢，且缺乏有效的分子靶向治疗手段。近年来，随着代谢重编程与表观遗传调控交叉机制研究的深入，一种新型的表观修饰形式——乳酸化修饰（Lysine lactylation，Kla）因在调控基因表达与细胞命运中的潜在作用而受到广泛关注。本文围绕乳酸代谢的调控机制与Kla的生物学功能，结合近年来在组蛋白乳酸化、内皮细胞代谢塑形及血管发育异常等方面的研究进展，系统阐述了Kla在调控血管生成、内皮细胞功能重构等过程中的作用，并进一步提出脉管畸形中常见的PIK3CA突变、糖酵解增强与微环境低氧等病理基础，可能是通过诱导乳酸积累与 Kla上调，影响转录调控与内皮行为，从而参与病变的发生发展。最后，通过结合现有数据，推演了 Kla在脉管畸形中的可能的调控机制，并提出今后应从空间组学、代谢组与表观组联合分析、体内功能验证模型构建等方向，深入探究乳酸化修饰在脉管畸形中的作用与应用前景，以期为探索代谢-表观调控轴在血管发育异常中的功能提供新的研究视角，并为脉管畸形的分子机制研究与靶向治疗策略研究提供理论基础。

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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.

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