《生命科学》 2023, 35(9): 1185-1191

内皮细胞代谢在血管新生中的作用研究

井　云¹ , 张晓培² , 王　冰³ , 李仕永^3,*

¹镇江高等专科学校，镇江 212038 ²南京科技职业学院，南京 210044 ³南京医科大学第四附属医院，南京 210031

摘　要：

血管生成是指从已有的毛细血管或毛细血管后静脉发展而形成新血管的过程。血管生成调控过程复杂，交错影响，多种基因和信号分子如血管内皮生长因子(vascular endothelial growth factor, VEGF) 家族、纤维母细胞生长因子(fibroblast growth factor, FGF) 家族、Notch 和 Wnt 信号通路、转化生长因子-β(transforming growth factor-β, TGF-β) 信号、血管生成素(angiotensin, Ang) 和Tie 信号系统等参与调控血管生成。除了遗传和分子信号外，血管生成还受到代谢机制的调节。在此，本文概述了目前对内皮细胞(endothelial cells, ECs) 各种代谢途径的认识及其对生理和病理性血管生成的影响。其中，糖酵解、脂肪酸氧化和氨基酸代谢是目前最为常见的代谢途径，ECs 主要依靠糖酵解产生ATP。糖酵解调节器6- 磷酸果糖激酶-2/2,6- 二磷酸果糖激酶3 (6-phosphofructo-2-kinase/fructose-2,6-diphosphatase 3, PFKFB3) 通过调控尖端细胞(Tip cells)和柄细胞(Stalk cells) 的平衡，来决定血管生成的方向，并促进迁移性尖端细胞的表型。另一方面，脂肪酸氧化(fatty acid oxidation, FAO) 通过为生物合成提供碳源调节柄细胞的增殖。多种氨基酸对血管内皮细胞同样具有重要调节作用。此外，血管生成还与磷酸戊糖途径、己糖胺生物合成途径、线粒体氧化磷酸化及多元醇、糖原合成途径等有关。

通讯作者：李仕永 , Email:lishiyong513@126.com

The research of endothelial cell metabolism in angiogenesis

JING Yun¹ , ZHANG Xiao-Pei² , WANG Bing³ , LI Shi-Yong^3,*

¹Zhenjiang College, Zhenjiang 212038, China ²Nanjing Polytechnic Institute, Nanjing 210044, China ³The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing 210031, China

Abstract:

Angiogenesis refers to the growth of new capillaries from pre-existing blood vessels or postcapillary veins. Angiogenesis is a rather complex physiological process involving multiple levels of intertwined regulation, such as VEGF family, FGF family, Notch and Wnt signaling pathway, TGF-β signaling pathway, Ang, Tie signaling system, and so on. In addition to genetic and molecular signaling, angiogenesis is also closely regulated by metabolic shifts in ECs. Herein, we overview various pathways of angiogenic metabolism and their impacts on physiological and pathological angiogenesis. As for ECs, glycolysis, amino acid metabolism, and fatty acid metabolism are the most common metabolic pathway, while ECs mainly rely on glycolysis to produce ATP. Glycolysis regulator PFKFB3 plays a critical role in regulating Tip cells and Stalk cells to determine the angiogenesis effect and promote migratory Tip cell phenotype. In addition, fatty acid oxidation (FAO) contributes to biosynthesis by providing carbon to regulate Stalk cell proliferation. Various amino acids also play an important regulatory role in the metabolism of vascular endothelial cells. Moreover, angiogenesis is also related to pentose phosphate pathway, hexosamine biosynthetic pathway, mitochondrial oxidative phosphorylation as well as the pathway of glycogen synthesis and polyol.

Communication Author：LI Shi-Yong , Email:lishiyong513@126.com