Circular RNA circCHFR downregulation protects against oxidized low-density lipoprotein-induced endothelial injury via regulation of microRNA-15b-5p/growth arrest and DNA damage inducible gamma.

Abstract

Atherosclerosis is the leading cause of coronary heart disease. In recent years, circ_0029589 (circCHFR) has been found to be associated with atherosclerosis development. However, the molecular mechanism of circCHFR action in atherosclerosis development is unknown. This study was aimed to investigate the function and action mechanism of circCHFR in atherosclerosis development. An atherosclerosis cell model was created by exposing human vascular endothelial cells (HUVECs) to oxidized low-density lipoprotein. The expression of circCHFR, microRNA(miR)-15b-5p, growth arrest and DNA damage inducible gamma (GADD45G), and their associated proteins was evaluated using quantitative reverse transcription-polymerase chain reaction and Western blotting. Additionally, cell viability, apoptosis, and cytokine levels were determined using Cell Counting Kit-8 (CCK8) assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. circCHFR expression was upregulated in patients with atherosclerosis and oxidized low-density lipoprotein (ox-LDL)-exposed HUVECs, whereas miR-15b-5p expression was downregulated. circCHFR silencing significantly improved viability and reduced apoptosis of HUVECs. In addition, the pro-apoptotic protein Bax and atherosclerosis-associated cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) were significantly downregulated, whereas the anti-apoptotic protein Bcl-2 was upregulated. Further, we discovered that circCHFR serves as a molecular sponge of miR-15b-5p. GADD45G was found to be an important target of miR-15b-5p; miR-15b-5p mimic inhibited GADD45G expression, reduced apoptosis and proinflammatory cytokine secretion, and improved cell survival. However, these effects of miR-15b-5p on (ox-LDL) induced HUVECs were reversed with GADD45G plasmid co-transfection. In conclusion, circCHFR promotes atherosclerosis progression via the miR-15b-5p/GADD45G axis and may be an important target for atherosclerosis treatment.

• Authors: Yang Li, Bing Wang
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 2 Pg. 4481-4492 (02 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35137664 (Publication Type: Journal Article)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Lipoproteins, LDL
• MIRN15 microRNA, human
• MicroRNAs
• RNA, Circular
• oxidized low density lipoprotein

Topics

• Atherosclerosis (metabolism)
• Cells, Cultured
• Down-Regulation (genetics)
• Endothelium (metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Lipoproteins, LDL (metabolism)
• MicroRNAs (genetics)
• RNA, Circular (genetics)
• GADD45 Proteins