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

Signal Transduction and Targeted Therapy

Article

Jia-Guo Zhou¹  Yi-Jun Lin²  Yang Cao²  Si Chen²  Ze-Long Liu²  Yu-Jia Liu²  Bi-Ang Kang²  Ya-Ting Chen²  Yan Li²  Yue-Ming Peng²  Le Li²  Zhen-Sheng Ma²  Jian-Jun Gao²  Meng-Jie Deng²  Zhi-Wei Mo³  Jing-Song Ou⁴  Mary G. Sorci-Thomas⁵  Zhan-Peng Huang⁶  Yu-Gang Dong⁷  Zhi-Jun Ou⁸  Yi-Xin Zhang⁸  Zuo-Jun Hu⁹  Guang-Qi Chang⁹  Mian Wang⁹ 

[1] Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine of Sun Yat-sen University, Guangzhou, China;Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;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;Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;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;Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;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;Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, P.R. China;Medical College of Wisconsin, Milwaukee, WI, USA;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;Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;Department of Cardiology, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;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;Department of Cardiology, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;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;Division of Hypertension and Vascular Diseases, Department of Cardiology, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;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;Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;

关键词: ;   

DOI  :  10.1038/s41392-023-01558-6

 received in 2022-09-08, accepted in 2023-07-09,  发布年份 2023

来源: Springer

【 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.

【 授权许可】

CC BY   
© West China Hospital, Sichuan University 2023

【 图 表 】

Fig. 5

Fig. 4

40538_2023_456_Article_IEq2.gif

Fig. 1

Fig. 2

Fig. 2

40517_2023_261_Article_IEq37.gif

13690_2023_1154_Article_IEq12.gif

Fig. 1