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High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA. Signal Transduct Target Ther 2023 Aug 14;8(1):299

Date

08/14/2023

Pubmed ID

37574469

Pubmed Central ID

PMC10423722

DOI

10.1038/s41392-023-01558-6

Scopus ID

2-s2.0-85168069378 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

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.

Author List

Mo ZW, Peng YM, Zhang YX, Li Y, Kang BA, Chen YT, Li L, Sorci-Thomas MG, Lin YJ, Cao Y, Chen S, Liu ZL, Gao JJ, Huang ZP, Zhou JG, Wang M, Chang GQ, Deng MJ, Liu YJ, Ma ZS, Hu ZJ, Dong YG, Ou ZJ, Ou JS

Author

Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Endothelial Cells
Humans
Lipoproteins, HDL
Mice
Neovascularization, Physiologic
Proliferating Cell Nuclear Antigen
RNA, Long Noncoding