CARDIOLOGY / EXPERIMENTAL RESEARCH
MiR-200a promotes the survival of cardiac cells and improves cardiac injury in chronic heart failure rats
More details
Hide details
1
Department of Cardiology, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China
2
Department of AIDS Prevention and Control, Taiyuan Center for Disease Control and Prevention, Taiyuan, Shanxi, China
Submission date: 2020-02-22
Final revision date: 2020-03-10
Acceptance date: 2020-03-12
Online publication date: 2020-04-19
Publication date: 2025-04-23
Corresponding author
Guiping Wu
Department of Cardiology, Shanxi Provincial
People’s Hospital, 29 Shuangtasi St, Taiyuan 030000, Shanxi, China
Arch Med Sci 2025;21(2):526-537
KEYWORDS
TOPICS
ABSTRACT
Introduction:
miRNAs play an important role in cardiovascular abnormalities such as heart failure. In the present work we evaluated the role of miR-200a in the condition of chronic heart failure and also the mechanism involved.
Material and methods:
In the study 180 subjects, among whom 100 were reported for chronic heart failure and 80 as normal, were included. ELISA and qRT-PCR was done to evaluate levels of HMGB1 and miR-200a in subjects. The cardiac hemodynamics and functioning, oxidative stress and expression of mediators of inflammation were studied in rats with chronic heart failure induced after transfecting them with miR-200a or HMGB1. Luciferase activity was measured to establish any correlation between HMGB1 and miR-200a.
Results:
The chronic heart failure patients included in the study showed suppressed levels of miR-200a and elevated HMGB1 compared to normal subjects. In chronic heart failure rats, the transfection of miR-200a attenuated the cardiac function and other hemodynamic parameters. In addition, improvement in oxidative stress as well as inflammatory mediators was observed. The outcomes also confirmed that HMGB1 was the potential target of miR-200a. It was also noted that upon transfection miR-200a resulted in suppression of protein as well as mRNA levels of HMGB1 in the cardiac tissue of chronic heart failure rats. Also overexpression of HMGB1 decreased the effects of miR-200a.
Conclusions:
The outcomes indicate that miR-200a exerts a protective effect on cardiac cell injury via the HMGB1 pathway.
REFERENCES (30)
1.
Inamdar AA, Inamdar AC. Heart failure: diagnosis, management and utilization. J Clin Med 2016; 5: E62.
2.
Savarese G, Lund LH. Global public health burden of heart failure. Cardiac Fail Rev 2017; 3: 7-11.
3.
Choi HM, Park MS, Youn JC. Update on heart failure management and future directions. Korean J Intern Med 2019; 34: 11-43.
4.
Azad N, Lemay G. Management of chronic heart failure in the older population. J Geriatr Cardiol 2014; 11: 329-37.
5.
Yan H, Ma F, Zhang Y, et al. miRNAs as biomarkers for diagnosis of heart failure: a systematic review and meta-analysis. Medicine (Baltimore) 2017; 96: e6825.
6.
Murach KA, McCarthy JJ. MicroRNAs, heart failure, and aging: potential interactions with skeletal muscle. Heart Fail Rev 2017; 22: 209-18.
7.
Di YF, Li DC, Shen YQ, et al. MiR-146b protects cardiomyocytes injury in myocardial ischemia/reperfusion by targeting Smad4. Am J Transl Res 2017; 9: 656-63.
8.
Rang Z, Wang Z, Pang Q, Wang Y, Yang G, Cui F. MiR-181a targets PHLPP2 to augment AKT signaling and regulate proliferation and apoptosis in human keloid fibroblasts. Cell Physiol Biochem 2016; 40: 796-806.
9.
Yang T, Cao C, Yang J, et al. miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11. Redox Biol 2018; 15: 159-69.
10.
Wang X, Huang S, Li X, et al. A potential biomarker hsa-miR-200a-5p distinguishing between benign thyroid tumors with papillary hyperplasia and papillary thyroid carcinoma. PLoS One 2018; 13: e0200290.
11.
Xiao H, Tang K, Liu P, et al. LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma. Oncotarget 2015; 6: 38005-15.
12.
Gao C, Peng FH, Peng LK. MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1. Neoplasma 2014; 61: 680-9.
13.
Li S, Huang Y, Huang Y, et al. The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation. J Exp Clin Cancer Res 2017; 36: 51.
14.
Kang R, Chen R, Zhang Q, et al. HMGB1 in health and disease. Mol Aspects Med 2014; 40: 1-116.
15.
Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V. How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC 2019; 30: 114-27.
16.
Yang L, Wang B, Zhou Q, et al. MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7. Cell Death Dis 2018; 9: 769.
17.
Aspromonte N, Gulizia MM, Clerico A, et al. ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure. Eur Heart J Suppl 2017; 19 (Suppl D): D102-12.
18.
Welsh P, Kou L, Yu C, et al. 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 2018; 20: 268-77.
19.
Wong LL, Armugam A, Sepramaniam S, et al. Circulating microRNAs in heart failure with reduced and preserved left ventricular ejection fraction. Eur J Heart Fail 2015; 17: 393-404.
20.
Sun X, Zuo H, Liu C, Yang Y. Overexpression of miR-200a protects cardiomyocytes against hypoxia-induced apoptosis by modulating the kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling axis. Int J Mol Med 2016; 38: 1303-11.
21.
Pellegrini L, Foglio E, Pontemezzo E, Germani A, Russo MA, Limana F. HMGB1 and repair: focus on the heart. Pharmacol Ther 2019; 196: 160-82.
22.
Li W, Sama AE, Wang H. Role of HMGB1 in cardiovascular diseases. Curr Opin Pharmacol 2006; 6: 130-5.
23.
Yao HC, Zhou M, Zhou YH, et al. 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 2016; 13: 1211-9.
24.
Lu Y, Lu J, Li X, et al. MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell. BMC Cancer 2014; 14: 85.
25.
Elahi MM, Kong YX, Matata BM. Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev 2009; 2: 259-69.
26.
Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP. Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals 2017; 11: E2.
27.
Mukhopadhyay P, Eid N, Abdelmegeed MA, Sen A. Interplay of oxidative stress, inflammation, and autophagy: their role in tissue injury of the heart, liver, and kidney. Oxid Med Cell Longev 2018; 2018: 2090813.
28.
Kozak J, Wdowiak P, Maciejewski R, Torres A. Interactions between microRNA-200 family and Sestrin proteins in endometrial cancer cell lines and their significance to anoikis. Mol Cell Biochem 2019; 459: 21-34.
29.
Li M, Li J, Ye C, Wu W, Cheng Y. miR-200a-3p predicts prognosis and inhibits bladder cancer cell proliferation by targeting STAT4. Arch Med Sci 2023; 19: 724-35.
30.
Martinotti S, Patrone M, Ranzato E. Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. Immunotargets Therapy 2015; 4: 101-9.