Abstract
Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p in chronic heart failure and the underlying mechanisms. The levels of miR-129-5p and HMGB1 in chronic heart failure patients (CHF) and normal controls were examined by RT-qPCR and ELISA. Cardiac function, hemodynamics parameters, oxidative stress, and inflammation factors were analyzed in CHF rat model after transfection of miR-129-5p or HMGB1. Dual-luciferase activity reporter assay was conducted to validate the interaction between miR-129-5p and HMGB1. Downregulation of miR-129-5p and upregulation of HMGB1 were observed in the serum of CHF patients, respectively. Transfection of miR-129-5p improved heart function and hemodynamic parameters, as well as attenuated oxidative stress and inflammation factors in CHF rats. We further confirmed that HMGB1 is a direct target of miR-129-5p. Transfection of miR-129-5p also decreased the mRNA and protein levels of HMGB1 in myocardial tissues of CHF rats. Overexpression of HMGB1 diminished the effects of miR-129-5p on ameliorating oxidative stress and inflammatory response in rats with CHF. Our findings suggest that miR-129-5p protects the heart by targeting HMGB1.
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References
Aspromonte N et al (2017) ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure. European Heart Journal Supplements 19:D102–D112. https://doi.org/10.1093/eurheartj/sux027
Azad N, Lemay G (2014) Management of chronic heart failure in the older population. J Geriatr Cardiol 11:329–337. https://doi.org/10.11909/j.issn.1671-5411.2014.04.008
Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V (2019) How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC 30:114–127
Buscaglia LE, Li Y (2011) Apoptosis and the target genes of microRNA-21. Chin J Cancer 30:371–380
Choi HM, Park MS, Youn JC (2019) Update on heart failure management and future directions. Korean J Intern Med 34:11–43. https://doi.org/10.3904/kjim.2018.428
Dinatolo E, Sciatti E, Anker MS, Lombardi C, Dasseni N, Metra M (2018) Updates in heart failure: what last year brought to us. ESC Heart Fail 5:989–1007. https://doi.org/10.1002/ehf2.12385
Elahi MM, Kong YX, Matata BM (2009) Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev 2:259–269. https://doi.org/10.4161/oxim.2.5.9441
Funahashi H, Izawa H, Hirashiki A, Cheng XW, Inden Y, Nomura M, Murohara T (2011) Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure. J Cardiol 57:338–344. https://doi.org/10.1016/j.jjcc.2011.01.009
Hu H, Zhang Y, Shi Y, Feng L, Duan J, Sun Z (2017) Microarray-based bioinformatics analysis of the combined effects of SiNPs and PbAc on cardiovascular system in zebrafish. Chemosphere 184:1298–1309. https://doi.org/10.1016/j.chemosphere.2017.06.112
Huang YM, Li WW, Wu J, Han M, Li BH (2019) The diagnostic value of circulating microRNAs in heart failure. Exp Ther Med 17:1985–2003. https://doi.org/10.3892/etm.2019.7177
Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP (2017) Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals. https://doi.org/10.3390/ph11010002
Inamdar AA, Inamdar AC (2016) Heart failure: diagnosis, management and utilization. J Clin Med. https://doi.org/10.3390/jcm5070062
Kalogeropoulos AP, Georgiopoulou VV, Butler J (2012) Clinical adoption of prognostic biomarkers: the case for heart failure. Prog Cardiovasc Dis 55:3–13. https://doi.org/10.1016/j.pcad.2012.05.004
Li W, Sama AE, Wang H (2006) Role of HMGB1 in cardiovascular diseases. Curr Opin Pharmacol 6:130–135. https://doi.org/10.1016/j.coph.2005.10.010
Li XQ, Chen FS, Tan WF, Fang B, Zhang ZL, Ma H (2017) Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3-cytokine pathway. J Neuroinflamm 14:205. https://doi.org/10.1186/s12974-017-0977-4
Li G, Xie J, Wang J (2019) Tumor suppressor function of miR-129-5p in lung cancer. Oncol Lett 17:5777–5783. https://doi.org/10.3892/ol.2019.10241
Luo J, Chen J, He L (2015) mir-129-5p attenuates irradiation-induced autophagy and decreases radioresistance of breast cancer cells by targeting HMGB1 medical science monitor. Int Med J Exp Clin Res 21:4122–4129. https://doi.org/10.12659/msm.896661
Ma XL, Li SY, Shang F (2017) Effect of microRNA-129-5p targeting HMGB1-RAGE signaling pathway on revascularization in a collagenase-induced intracerebral hemorrhage rat model. Biomed Pharmacother 93:238–244. https://doi.org/10.1016/j.biopha.2017.06.012
Martinotti S, Patrone M, Ranzato E (2015) Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. ImmunoTargets Therapy 4:101–109. https://doi.org/10.2147/ITT.S58064
Motiejunaite J, Chouihed T, Mebazaa A (2017) Upcoming challenges in multidisciplinary heart failure management: active role of future clinical pharmacists. Clin Pharmacol Ther 102:180–182. https://doi.org/10.1002/cpt.728
Mukhopadhyay P, Eid N, Abdelmegeed MA, Sen A (2018) Interplay of oxidative stress, inflammation, and autophagy: their role in tissue injury of the heart, liver, and kidney. Oxid Med Cell Longev 2018:2090813. https://doi.org/10.1155/2018/2090813
Murach KA, McCarthy JJ (2017) MicroRNAs, heart failure, and aging: potential interactions with skeletal muscle. Heart Fail Rev 22:209–218. https://doi.org/10.1007/s10741-016-9572-5
Oikonomou E et al (2013) Diagnostic and therapeutic potentials of microRNAs in heart failure. Curr Top Med Chem 13:1548–1558
Pan Z et al (2012) miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models. PLoS ONE 7:e50515. https://doi.org/10.1371/journal.pone.0050515
Pashkow FJ (2011) Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention? Int J Inflamm 2011:514623. https://doi.org/10.4061/2011/514623
Qin Y, Yu Y, Dong H, Bian X, Guo X, Dong S (2012) MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis. Int J Med Sci 9:413–423. https://doi.org/10.7150/ijms.4514
Ramachandran S, Lowenthal A, Ritner C, Lowenthal S, Bernstein HS (2017) Plasma microvesicle analysis identifies microRNA 129-5p as a biomarker of heart failure in univentricular heart disease. PLoS ONE 12:e0183624. https://doi.org/10.1371/journal.pone.0183624
Ramani GV, Uber PA, Mehra MR (2010) Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc 85:180–195. https://doi.org/10.4065/mcp.2009.0494
Raucci A, Di Maggio S, Scavello F, D’Ambrosio A, Bianchi ME, Capogrossi MC (2019) The Janus face of HMGB1 in heart disease: a necessary update. Cell Mol Life Sci 76:211–229. https://doi.org/10.1007/s00018-018-2930-9
Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3:99–126. https://doi.org/10.1146/annurev.pathmechdis.3.121806.151456
Savarese G, Lund LH (2017) Global public health burden of heart failure. Cardiac Fail Rev 3:7–11. https://doi.org/10.15420/cfr.2016:25:2
Shah RV, Das S, Lewis GD (2019) Circulating microRNAs: new avenues for heart failure classification? J Am Coll Cardiol 73:1314–1316. https://doi.org/10.1016/j.jacc.2018.10.091
Silva D, Carneiro FD, Almeida KC, Fernandes-Santos C (2018) Role of miRNAs on the pathophysiology of cardiovascular diseases. Arq Bras Cardiol 111:738–746. https://doi.org/10.5935/abc.20180215
Verjans R et al (2019) Functional screening identifies micrornas as multi-cellular regulators of heart failure. Scientific Reports 9:6055. https://doi.org/10.1038/s41598-019-41491-9
Voellenkle C et al (2010) MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genom 42:420–426. https://doi.org/10.1152/physiolgenomics.00211.2009
Volz HC et al (2012) HMGB1 is an independent predictor of death and heart transplantation in heart failure. Clin Res Cardiol 101:427–435. https://doi.org/10.1007/s00392-011-0409-x
Wang S, Chen Y, Yu X, Lu Y, Wang H, Wu F, Teng L (2019) miR-129-5p attenuates cell proliferation and epithelial mesenchymal transition via HMGB1 in gastric cancer. Pathol Res Pract 215:676–682. https://doi.org/10.1016/j.prp.2018.12.024
Welsh P et al (2018) Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study. Eur J Heart Fail 20:268–277. https://doi.org/10.1002/ejhf.988
Wu Q, Meng WY, Jie Y, Zhao H (2018) LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1 axis. J Cell Physiol 233:6750–6757. https://doi.org/10.1002/jcp.26383
Yan H et al (2017) miRNAs as biomarkers for diagnosis of heart failure: a systematic review and meta-analysis. Medicine 96:e6825. https://doi.org/10.1097/MD.0000000000006825
Yang Y et al (2017) miRNAs as potential therapeutic targets and diagnostic biomarkers for cardiovascular disease with a particular focus on WO2010091204. Expert Opin Ther Pat 27:1021–1029. https://doi.org/10.1080/13543776.2017.1344217
Yang L, Wang B, Zhou Q, Wang Y, Liu X, Liu Z, Zhan Z (2018) MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7. Cell Death Dis 9:769. https://doi.org/10.1038/s41419-018-0805-5
Yao HC et al (2016) Intravenous high mobility group box 1 upregulates the expression of HIF-1alpha in the myocardium via a protein kinase B-dependent pathway in rats following acute myocardial ischemia. Mol Med Rep 13:1211–1219. https://doi.org/10.3892/mmr.2015.4648
Zhang D et al (2017a) Long noncoding RNA PCAT-1 promotes invasion and metastasis via the miR-129-5p-HMGB1 signaling pathway in hepatocellular carcinoma. Biomed Pharmacother 95:1187–1193. https://doi.org/10.1016/j.biopha.2017.09.045
Zhang J et al (2017b) Circulating miRNA21 is a promising biomarker for heart failure. Mol Med Rep 16:7766–7774. https://doi.org/10.3892/mmr.2017.7575
Zhang H, Zhang X, Zhang J (2018) MiR-129-5p inhibits autophagy and apoptosis of H9c2 cells induced by hydrogen peroxide via the PI3K/AKT/mTOR signaling pathway by targeting ATG14. Biochem Biophys Res Commun 506:272–277. https://doi.org/10.1016/j.bbrc.2018.10.085
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Xiao, N., Zhang, J., Chen, C. et al. miR-129-5p improves cardiac function in rats with chronic heart failure through targeting HMGB1. Mamm Genome 30, 276–288 (2019). https://doi.org/10.1007/s00335-019-09817-0
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DOI: https://doi.org/10.1007/s00335-019-09817-0