A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis

作者全名：Fan, Wei; Zeng, Shuhao; Wang, Xiaotang; Wang, Guoqing; Liao, Dan; Li, Ruonan; He, Siyuan; Li, Wanqian; Huang, Jiaxing; Li, Xingran; Liu, Jiangyi; Li, Na; Hou, Shengping

作者地址：[Fan, Wei; Zeng, Shuhao; Wang, Xiaotang; Wang, Guoqing; Liao, Dan; Li, Ruonan; He, Siyuan; Li, Wanqian; Huang, Jiaxing; Li, Xingran; Liu, Jiangyi; Hou, Shengping] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Li, Na] Capital Med Univ, Beijing Tongren Hosp, Dept Lab Med, Beijing 100005, Peoples R China; [Hou, Shengping] Capital Med Univ, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing Tongren Eye Ctr,Beijing Ophthalmol & Visua, Beijing 100730, Peoples R China

通信作者：Hou, SP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China.; Li, N (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Dept Lab Med, Beijing 100005, Peoples R China.; Hou, SP (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing Tongren Eye Ctr,Beijing Ophthalmol & Visua, Beijing 100730, Peoples R China.

来源：GENOME BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001254163600001

JCR分区：Q1

影响因子：10.1

年份：2024

卷号：25

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Angiogenesis; Endothelial cells (ECs); Histone deacetylase 2 (HDAC2); VEGF

摘要：BackgroundVascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis.ResultsHere, we show that a feedback loop between H3K9 lactylation (H3K9la) and histone deacetylase 2 (HDAC2) in endothelial cells drives VEGF-induced angiogenesis. We find that the H3K9la levels are upregulated in endothelial cells in response to VEGF stimulation. Pharmacological inhibition of glycolysis decreases H3K9 lactylation and attenuates neovascularization. CUT& Tag analysis reveals that H3K9la is enriched at the promoters of a set of angiogenic genes and promotes their transcription. Interestingly, we find that hyperlactylation of H3K9 inhibits expression of the lactylation eraser HDAC2, whereas overexpression of HDAC2 decreases H3K9 lactylation and suppresses angiogenesis.ConclusionsCollectively, our study illustrates that H3K9la is important for VEGF-induced angiogenesis, and interruption of the H3K9la/HDAC2 feedback loop may represent a novel therapeutic method for treating pathological neovascularization.

基金机构：National Natural Science Foundation Project of China [82070951, 82271078, 82371045]; Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (PWDRPP-MRI) [JYY2023-6]; Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]

基金资助正文：This work was supported by the National Natural Science Foundation Project of China (82070951, 82271078, 82371045), Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (PWD&RPP-MRI, JYY2023-6) and Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003).