High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA  

作　　者：Zhi-Wei Mo Yue-Ming Peng Yi-Xin Zhang Yan Li Bi-Ang Kang Ya-Ting Chen Le Li Mary GSorci-Thomas Yi-Jun Lin Yang Cao Si Chen Ze-Long Liu Jian-Jun Gao Zhan-Peng Huang Jia-Guo Zhou Mian Wang Guang-Qi Chang Meng-Jie Deng Yu-Jia Liu Zhen-Sheng Ma Zuo-Jun Hu Yu-Gang Dong Zhi-Jun Ou Jing-Song Ou 

机构地区：[1]Division of Cardiac Surgery,Cardiovascular Diseases Institute,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,China [2]National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases,NHC Key Laboratory of Assisted Circulation(Sun Yat-sen University),Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases,Guangzhou,China [3]Division of Vascular Surgery,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,China [4]Division of Hypertension and Vascular Diseases,Department of Cardiology,Heart Center,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,China [5]Medical College of Wisconsin,Milwaukee,WI,USA [6]Center for Translational Medicine,Institute of Precision Medicine,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,China [7]Department of Cardiology,Heart Center,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,China [8]Department of Pharmacology,Cardiac and Cerebral Vascular Research Center,Zhongshan School of Medicine of Sun Yat-sen University,Guangzhou,China [9]Guangdong Provincial Key Laboratory of Brain Function and Disease,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,P.R.China

出　　处：《Signal Transduction and Targeted Therapy》2023年第9期4320-4337,共18页信号转导与靶向治疗（英文）

基　　金：This research was financially supported by the National Key R&D Program of China 2021YFA0805100;National Natural Science Foundation of China(Grant Nos.92268202,81830013,81970363,82270485,and 81770241);Guangdong Basic and Applied Basic Research Foundation(Grant 2019B1515120092);Science and Technology Planning Project of Guangzhou,China 202103000016;Sun Yat-sen University Clinical Research 5010 Program(2014002);the Program of National Key Clinical Specialties.Figures 7a,8d and Supplementary Fig.S14a were created with BioRender.com.

摘　　要：Normal high-density lipoprotein(nHDL)can induce angiogenesis in healthy individuals.However,HDL from patients with coronary artery disease undergoes various modifications,becomes dysfunctional(dHDL),and loses its ability to promote angiogenesis.Here,we identified a long non-coding RNA,HDRACA,that is involved in the regulation of angiogenesis by HDL.In this study,we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2,which catalyzes the ubiquitination and subsequent degradation of its transcription factor,Kruppel-like factor 5,via sphingosine 1-phosphate(S1P)receptor 1.In contrast,dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA.HDRACA was able to bind to Ras-interacting protein 1(RAIN)to hinder the interaction between RAIN and vigilin,which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen(PCNA)mRNA,resulting in a decrease in the expression of PCNA and inhibition of angiogenesis.The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis.Taken together,these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis,which nHDL inhibits the expression of HDRACA to induce angiogenesis,and that dHDL is much less effective in inhibiting HDRACA expression,which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.

关 键 词：ANGIOGENESIS LIPOPROTEIN inhibited 

分 类 号：R543[医药卫生—心血管疾病]