Preliminary study on the role of miR-16 in progression of coronary atherosclerosis and possible molecular mechanism

doi:10.16150/j.1671-2870.2021.01.013

Abstract

Abstract:

Objective: To explore the role of microRNA (miRNA, miR) -16 in the development of coronary atheromatous plaques and to study possible mechanism involved in the process. Methods: Coronary artery tissues were obtained from 16 patients undergoing coronary artery bypass grafting,and the coronary artery plaques were divided into fibrous plaques and atheromatous plaques based on pathological examination. The expression level of miR-16 in coronary fibrous plaques and atheromatous plaques was detected by miRNAs array. The in vitro model of oxidized low density lipoprotein (oxLDL)-induced foam cells from macrophages was established, the transformation as well as apoptosis of foam cells were detected by TUNEL assay, cell counting and Western blotting. The release of inflammatory cytokines [interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9] in the culture supernatant of form cell was tested by enzyme-linked immunosorbent assay(ELISA), and expression of miR-16 was tested by miRNAs array. Finally, miR-16 was transfected into macrophages and the apoptosis of foam cell as well as the release of inflammatory factors were detected. Results: Compared with fibrous plaques of coronary artery, the expression of miR-16 in coronary atheromatous plaques detected by miRNAs assay increased by 1.75 folds. In vitro model of oxLDL-induced foam cells showed that oxLDL might promote the transfer of macrophages into foam cells and induce foam cells apoptosis and stimulate the release of inflammatory factors (such as IL-6, IL-8, MCP-1 and MMP-9). Macrophages transfected with miR-16 could further induce the apoptosis of foam cells and secretion of inflammatory factors. Conclusions: oxLDL could induce the apoptosis of foam cells, release of inflammatory factors and up-regulate miR-16 expression, and the high expression of miR-16 could further enhance foam cell apoptosis and inflammatory response, further promote the progression of atherosclerosis. miR-16 might serve as a potential target for inhibiting artherosclerosis.

Key words: miR-16, Atheromatous plaque, Foam cell, Apoptosis, Inflammatory response

CLC Number:

R541.4

ZHA Qing, YU Chenxi, LIU Ya, YANG Ling, YE Jiawen, LIU Yan. Preliminary study on the role of miR-16 in progression of coronary atherosclerosis and possible molecular mechanism[J]. Journal of Diagnostics Concepts & Practice, 2021, 20(01): 82-87.

Figures/Tables 6

References 26

[1]	Libby P, Theroux P. Pathophysiology of coronary artery disease[J]. Circulation, 2005, 111(25):3481-3488. doi: 10.1161/CIRCULATIONAHA.105.537878 URL
[2]	中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2019概要[J]. 中国循环杂志, 2020, 35(9):833-854.
[3]	Khera AV, Kathiresan S. Genetics of coronary artery di-sease: discovery, biology and clinical translation[J]. Nat Rev Genet, 2017, 18(6):331-344. doi: 10.1038/nrg.2016.160 pmid: 28286336
[4]	Lusis AJ. Atherosclerosis[J]. Nature, 2000, 407(6801):233-241. doi: 10.1038/35025203 URL
[5]	Frostegård J. Immunity, atherosclerosis and cardiovascular disease[J]. BMC Med, 2013, 11:117. doi: 10.1186/1741-7015-11-117 pmid: 23635324
[6]	Kattoor AJ, Kanuri SH, Mehta JL. Role of Ox-LDL and LOX-1 in atherogenesis[J]. Curr Med Chem, 2019, 26(9):1693-1700. doi: 10.2174/0929867325666180508100950 pmid: 29737246
[7]	Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture[J]. Circ Res, 2014, 114(12):1852-1866. doi: 10.1161/CIRCRESAHA.114.302721 pmid: 24902970
[8]	Laffont B, Rayner KJ. MicroRNAs in the pathobiology and therapy of atherosclerosis[J]. Can J Cardiol, 2017, 33(3):313-324. doi: S0828-282X(17)30001-6 pmid: 28232017
[9]	Lu Y, Thavarajah T, Gu W, et al. Impact of miRNA in atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2018, 38(9):e159-e170.
[10]	Yang K, He YS, Wang XQ, et al. MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4[J]. FEBS Lett, 2011, 585(6):854-860. doi: 10.1016/j.febslet.2011.02.009 pmid: 21329689
[11]	Wang M, Li J, Cai J, et al. Overexpression of MicroRNA-16 alleviates atherosclerosis by inhibition of inflammatory pathways[J]. Biomed Res Int, 2020, 2020:8504238.
[12]	O Sullivan JF, Neylon A, McGorrian C, et al. miRNA-93-5p and other miRNAs as predictors of coronary artery disease and STEMI[J]. Int J Cardiol, 2016, 224:310-316. doi: S0167-5273(16)32196-9 pmid: 27665403
[13]	Di Pietro N, Formoso G, Pandolfi A. Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis[J]. Vascul Pharmacol, 2016, 84:1-7. doi: 10.1016/j.vph.2016.05.013 URL
[14]	Gisterå A, Hansson GK. The immunology of atherosclerosis[J]. Nat Rev Nephrol, 2017, 13(6):368-380. doi: 10.1038/nrneph.2017.51 pmid: 28392564
[15]	Guo JF, Zhang Y, Zheng QX, et al. Association between elevated plasma microRNA-223 content and severity of coronary heart disease[J]. Scand J Clin Lab Invest, 2018, 78(5):373-378. doi: 10.1080/00365513.2018.1480059 URL
[16]	Bao MH, Li GY, Huang XS, et al. Long noncoding RNA LINC00657 acting as a miR-590-3p sponge to facilitate low concentration oxidized low-density lipoprotein-induced angiogenesis[J]. Mol Pharmacol, 2018, 93(4):368-375. doi: 10.1124/mol.117.110650 URL
[17]	Jiang W, Li T, Wang J, et al. miR-140-3p Suppresses cell growth and induces apoptosis in colorectal cancer by targeting PD-L1[J]. Onco Targets Ther, 2019, 12:10275-10285. doi: 10.2147/OTT.S226465 URL
[18]	Yan L, Cai K, Sun K, et al. MiR-1290 promotes prolife-ration, migration, and invasion of glioma cells by targe-ting LHX6[J]. J Cell Physiol, 2018, 233(10):6621-6629. doi: 10.1002/jcp.26381 URL
[19]	Zhou R, Li X, Hu G, et al. miR-16 targets transcriptional corepressor SMRT and modulates NF-kappaB-regulated transactivation of interleukin-8 gene[J]. PLoS One, 2012, 7(1):e30772. doi: 10.1371/journal.pone.0030772 URL
[20]	Jing Q, Huang S, Guth S, et al. Involvement of microRNA in AU-rich element-mediated mRNA instability[J]. Cell, 2005, 120(5):623-634. doi: 10.1016/j.cell.2004.12.038 URL
[21]	Krogmann AO, Lüsebrink E, Steinmetz M, et al. Proinflammatory stimulation of Toll-like receptor 9 with high dose CpG ODN 1826 impairs endothelial regeneration and promotes atherosclerosis in mice[J]. PLoS One, 2016, 11(1):e0146326. doi: 10.1371/journal.pone.0146326 URL
[22]	Satoh M, Takahashi Y, Tabuchi T, et al. Circulating Toll-like receptor 4-responsive microRNA panel in patients with coronary artery disease: results from prospective and randomized study of treatment with renin-angiotensin system blockade[J]. Clin Sci (Lond), 2015, 128(8):483-491. doi: 10.1042/CS20140417 URL
[23]	Lin F, Pei L, Zhang Q, et al. Ox-LDL induces endothelial cell apoptosis and macrophage migration by regulating caveolin-1 phosphorylation[J]. J Cell Physiol, 2018, 233(10):6683-6692. doi: 10.1002/jcp.26468 URL
[24]	Borghi A, Verstrepen L, Beyaert R. TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death[J]. Biochem Pharmacol, 2016, 116:1-10. doi: 10.1016/j.bcp.2016.03.009 pmid: 26993379
[25]	Chen T, Xiao Q, Wang X, et al. miR-16 regulates proli-feration and invasion of lung cancer cells via the ERK/MAPK signaling pathway by targeted inhibition of MAPK kinase 1(MEK1)[J]. J Int Med Res, 2019, 47(10):5194-5204. doi: 10.1177/0300060519856505 URL
[26]	Pekarsky Y, Balatti V, Croce CM. BCL2 and miR-15/16: from gene discovery to treatment[J]. Cell Death Differ, 2018, 25(1):21-26. doi: 10.1038/cdd.2017.159 pmid: 28984869