溶血磷脂酸在血管内皮细胞中作用的分子机制及潜在临床价值

Molecular Mechanism and Potential Clinical Value of Lysophosphatidic Acid in Vascular Endothelial Cells

血管系统构成了人体最大的表面。血管内皮细胞是覆盖于血管内壁的一层扁平上皮细胞,具有内分泌、血管生成和构成生物屏障等多种生物学功能,在维持血管系统稳态和机体正常生命活动中至关重要。溶血磷脂酸(lysophosphatidic acid,LPA)是一种活跃的磷脂信号分子,可以促进血管内皮细胞产生趋化因子和黏附分子,还可以调节血管内皮细胞间的连接和血管生成。本文以LPA在血管内皮细胞中的作用为切入点,综述了近年来LPA在血管内皮细胞中作用的分子机制。LPA通过上调血管内皮细胞趋化因子和黏附分子的表达,在白细胞的募集、滚动和黏附中发挥重要作用;LPA通过调节血管内皮细胞间的连接,在调节血管壁通透性方面发挥重要作用;LPA通过调节血管内皮细胞的形态、行为和功能,在血管生成和成熟中发挥作用。此外,还综述了LPA在血管内皮细胞功能失调中的潜在临床价值,包括在新型冠状病毒肺炎、动脉粥样硬化、脑缺血再灌注、阿尔兹海默病、肿瘤和糖尿病中的临床价值。目前,LPA在血管内皮细胞中的详细作用机制尚未完全阐明,深入研究LPA在血管内皮细胞中的受体表达、生物学作用及调控机制,将为血管内皮功能失调的治疗提供新的策略。

The vascular system constitutes the largest surface of the human body.Vascular endothelial cells are a layer of flat epithelial cells covering the inner wall of blood vessels and have a variety of biological functions such as endocrine,angiogenesis and forming a biological barrier.Therefore,vascular endothelial cells are very important in maintaining the homeostasis of vascular system and normal life activities of the body.Lysophosphatidic acid(LPA),as a bioactive phospholipid messenger,can promote the production of chemokines and adhesion molecules in vascular endothelial cells.LPA also regulate vascular permeability and angiogenesis.Based on the role of LPA in vascular endothelial cells,we review the molecular mechanism of LPA in vascular endothelial cells in recent years.Firstly,LPA plays an important role in leukocyte recruitment,rolling and adhesion by increasing the expression of vascular endothelial chemokines and adhesion molecules.Secondly,LPA has a role in regulating vascular wall permeability by adjusting the connections between vascular endothelial cells.Finally,LPA plays a role in angiogenesis and vascular maturation by regulating the morphology,behavior,and function of vascular endothelial cells.Inaddition,we also review the potential clinical value of LPA in vascular endothelial dysfunction,such as COVID-19,atherosclerosis,cerebral ischemia reperfusion,Alzheimer’s disease,tumor,and diabetes.At present,the detailed mechanism of LPA in vascular endothelial cells has not been fully clarified.Further study of LPA receptor expression in vascular endothelial cells and molecular regulatory mechanism will provide new strategies for the treatment of vascular endothelial dysfunction.