Myricetin ameliorates ox-LDL-induced HUVECs apoptosis and inflammation via lncRNA GAS5 upregulating the expression of miR-29a-3p

• Published in: Scientific reports Vol. 11; no. 1; p. 19637
• Main Authors: Bai, Yunpeng, Liu, Xiankun, Chen, Qingliang, Chen, Tongyun, Jiang, Nan, Guo, Zhigang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-10-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 692/699; Antioxidants; Apoptosis; Apoptosis - drug effects; Arteriosclerosis; Atherosclerosis; Biomarkers; Endothelial cells; Flavonoids - pharmacology; Flow cytometry; Fluorescence in situ hybridization; Gene Expression Regulation - drug effects; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humanities and Social Sciences; Humans; Immunocytochemistry; Immunophenotyping; Immunoprecipitation; Inflammation; Inflammation - etiology; Inflammation - metabolism; Lipoproteins, LDL - metabolism; Low density lipoprotein; MicroRNAs - genetics; Models, Biological; multidisciplinary; NF-kappa B - metabolism; NF-κB protein; Overexpression; Polymerase chain reaction; Reactive Oxygen Species - metabolism; RNA Interference; RNA, Long Noncoding - genetics; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - drug effects; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-98916-7

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell dysfunction is a significant event in the progression of atherosclerosis. Even Myricetin (Myr) has been exhibited strong antioxidant potency, the effect on atherosclerosis is still elusive. HUVECs were subjected to ox-LDL, before which cells were preconditioned with Myr. Cell Counting Kit-8 assay, flow cytometry, quantitative real-time polymerase chain reaction and Western blot were carried out to assess the impacts of ox-LDL and Myr on HUVECs. The expression of EndMT markers was determined by Western blot analysis and immunocytochemistry. In addition, the relationship of GAS5 and miR-29a-3p was evaluated by RNA Fluorescent in Situ Hybridization and RNA immunoprecipitation assay. Myr preconditioning prevented ox-LDL-induced apoptosis, inflammatory response, and EndMT. GAS5 was upregulated in response to ox-LDL while it was down-regulated by Myr preconditioning. GAS5 over-expression attenuates Myr protective effects against ox-LDL–mediated HUVEC injury. Besides, miR-29a-3p is a target of GAS5 and down-regulated miR-29a-3p could further reduce the effects of GAS5 in ox-LDL–mediated HUVEC. Furthermore, Myr inactivated the TLR4/NF-κB signalling pathway in ox-LDL-treated HUVEC by down-regulating GAS5 or upregulating miR-26a-5p. Myr possessed an anti-inflammatory and anti-EndMT function against ox-LDL-induced HUVEC injury by regulating the GAS5/miR-29a-3p, indicating that Myr may have an important therapeutic function for atherosclerosis.