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The roles of miR-101, miR-1183 and miR-1299 in acute rheumatic fever and rheumatic heart disease

Published online by Cambridge University Press:  03 February 2025

Ece Korkmaz Open the ORCID record for Ece Korkmaz [Opens in a new window] ,
Dolunay Gürses Open the ORCID record for Dolunay Gürses [Opens in a new window] ,
Gökhan Çetin  and
Hande Senol
Ece Korkmaz
Affiliation:
Department of Pediatrics, Pamukkale University, Denizli, Turkey
Dolunay Gürses*
Affiliation:
Department of Pediatric Cardiology, Pamukkale University Faculty of Medicine, Denizli, Turkey
Gökhan Çetin
Affiliation:
Department of Medical Genetics, Pamukkale University, Denizli, Turkey
Hande Senol
Affiliation:
Department of Biostatistics, Pamukkale University, Denizli, Turkey
*
Corresponding author: Dolunay Gürses; Email: dolunayk@yahoo.com
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Abstract

Introduction:

Acute rheumatic fever commonly causes carditis in children. It is critical to have biomarkers for diagnostic and prognostic purposes. We aimed to investigate the expressions of miR-101, miR-1183, and miR-1299 in children with acute rheumatic fever and rheumatic heart disease and determine their potential as diagnostic biomarkers.

Methods:

This cross-sectional study was conducted on 69 paediatric acute rheumatic fever patients and 27 gender and age-matched controls. The clinical findings were noted from medical records, echocardiography was repeated, and plasma miR-101, miR-1183, and miR-1299 expressions were studied using RT-PCR.

Results:

Out of 54 patients with carditis, 36 developed rheumatic heart disease with significant left-sided heart involvement. No significant demographic difference was present between rheumatic heart disease patients and controls (p > 0.05). miR-101 and miR-1183 expressions significantly reduced by 4.5-fold in acute rheumatic fever patients compared to controls (p : 0.029 and p : 0.024, respectively). Family history was found to be significantly associated with 9-fold reduced miR-1183 expression in acute rheumatic fever patients (p : 0.005). The expression of miR-1183 in acute rheumatic fever children with carditis in general and severe carditis was significantly reduced 4.5- and 9-fold, respectively (p : 0.024 and p : 0.007, respectively). In acute rheumatic fever cases with moderate-severe carditis and patients who did not develop rheumatic heart disease, miR-1183 expression significantly reduced 8.3-fold and 9-fold, respectively (p : 0.015 and p : 0.019, respectively). The ROC analysis revealed that miR-101 and miR-1183 were statistically significant for acute rheumatic fever diagnosis (AUC: 0.64 for both miRNAs).

Conclusions:

Significantly lower plasma expressions of miR-101 and miR-1183 in acute rheumatic fever patients, especially in cases with moderate-severe carditis, might indicate the potential use of these miRNAs as diagnostic biomarkers.

Keywords

Acute rheumatic feverrheumatic heart diseasemiRNAcarditis
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 8
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Copyright
© The Author(s), 2025. Published by Cambridge University Press

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References

Arvind, B, Ramakrishnan, S. Rheumatic fever and rheumatic heart disease in children. Indian J Pediatr 2020; 87: 305–311. DOI: 10.1007/s12098-019-03128-7.CrossRefGoogle ScholarPubMed
Watkins, DA, Johnson, CO, Colquhoun, SM et al. Global, regional, and national burden of rheumatic heart disease, 1990–2015. N Engl J Med 2017; 377: 713–722. DOI: 10.1056/NEJMoa1603693.CrossRefGoogle ScholarPubMed
Gewitz, MH, Baltimore, RS, Tani, LY et al. Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography. Circulation 2015; 131: 1806–1818. DOI: 10.1161/CIR.0000000000000205.CrossRefGoogle Scholar
Reményi, B, Wilson, N, Steer, A et al. World heart federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline. Nat Rev Cardiol 2012; 9: 297–309. DOI: 10.1038/nrcardio.2012.7.CrossRefGoogle ScholarPubMed
Bright, PD, Mayosi, BM, Martin, WJ. An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers. Heart 2016; 102 1527–1532. DOI: 10.1136/heartjnl-2015-309188.CrossRefGoogle ScholarPubMed
Yousry, SM, Sedky, Y, Sobieh, A. Association of IL-4 (intron 3) and IL-10 (−1082) gene polymorphisms with risk of mitral valve disease in children with rheumatic heart disease. Cardiol Young 2016; 26: 1290–1296. DOI: 10.1017/S1047951115002413.CrossRefGoogle Scholar
Catarino, SJ, Andrade, FA, Boldt, ABW et al. Sickening or healing the heart? The association of ficolin-1 and rheumatic fever. Front Immunol 2018; 9: 3009. DOI: 10.3389/fimmu.2018.03009.CrossRefGoogle ScholarPubMed
Zheng, D, Chen, X, Li, N et al. Differentially methylated regions in patients with rheumatic heart disease and secondary pulmonary arterial hypertension. Exp Ther Med 2017; 14: 1367–1372. DOI: 10.3892/etm.2017.4652.CrossRefGoogle ScholarPubMed
Asulin, N, Volinsky, N, Grosman-Rimon, L et al. Differential microRNAs expression in calcified versus rheumatic aortic valve disease. J Card Surg 2020; 35: 1508–1513. DOI: 10.1111/jocs.14636.CrossRefGoogle ScholarPubMed
Çakmak, HA, Demir, M. MicroRNA and cardiovascular diseases. Balkan Med J 2020; 37: 60–71. DOI: 10.4274/balkanmedj.galenos.2020.2020.1.94.Google ScholarPubMed
Song, Y, Higgins, H, Guo, J et al. Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children. J Transl Med 2018; 16: 42. DOI: 10.1186/s12967-018-1411-0.CrossRefGoogle ScholarPubMed
Siddeek, B, Mauduit, C, Yzydorczyk, C et al. At the heart of programming: the role of micro-RNAs. J Dev Orig Health Dis 2018; 9: 615–631. DOI: 10.1017/S2040174418000387.CrossRefGoogle ScholarPubMed
Wang, W, Zhang, Y, Zhu, B et al. Plasma microRNA expression profiles in Chinese patients with rheumatoid arthritis. Oncotarget 2015; 6: 42557–42568. DOI: 10.18632/oncotarget.6449.CrossRefGoogle ScholarPubMed
Chen, A, Wen, J, Lu, C et al. Inhibition of miR-155-5p attenuates the valvular damage induced by rheumatic heart disease. Int J Mol Med 2020; 45: 429–440. DOI: 10.3892/ijmm.2019.4420.Google ScholarPubMed
Lu, Q, Sun, Y, Duan, Y et al. Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease. BMC Cardiovasc Disord 2018; 18: 53. DOI: 10.1186/s12872-018-0788-2.CrossRefGoogle ScholarPubMed
Gumus, G, Giray, D, Bobusoglu, O et al. MicroRNA values in children with rheumatic carditis: a preliminary study. Rheumatol Int 2018; 38: 1199–1205. DOI: 10.1007/s00296-018-4069-2.CrossRefGoogle ScholarPubMed
Dong, H, Sun, Y, Shan, F et al. Down-regulation of miR-101 contributes to rheumatic heart disease through up-regulating TLR2. Med Sci Monit 2015; 21: 1500–1506. https://dx.doi.org/10.12659/MSM.893540.Google ScholarPubMed
Li, N, Lian, J, Zhao, S et al. Detection of differentially expressed MicroRNAs in rheumatic heart disease: miR-1183 and miR-1299 as potential diagnostic biomarkers. Biomed Res Int 2015; 2015: 1–11. DOI: 10.1155/2015/524519 Google ScholarPubMed
Heart Foundation New Zealand. Algorithm 3: guide for the duration of secondary prophylaxis in acute rheumatic fever (ARF) 2020. https://assets.heartfoundation.org.nz/documents/shop/heart-healthcare/non-stock-resources/secondary-prophylaxis-rheumatic-fever-algorithm.pdf.Google Scholar
Zhao, X, Wang, K, Liao, Y et al. MicroRNA-101a inhibits cardiac fibrosis induced by hypoxia via targeting TGFβRI on cardiac fibroblasts. Cell Physiol Biochem 2015; 35: 213–226. DOI: 10.1159/000369689.CrossRefGoogle ScholarPubMed
Balashanmugam, MV, Shivanandappa, TB, Nagarethinam, S et al. Analysis of differentially expressed genes in coronary artery disease by integrated microarray analysis. Biomolecules 2020; 10: 35. DOI: 10.3390/biom10010035.CrossRefGoogle Scholar
Pokhrel, S, Guotian, Y. MicroRNA and its role in cardiovascular disease. World J Cardiovasc Dis 2017; 7: 340–357. DOI: 10.4236/wjcd.2017.710032.CrossRefGoogle Scholar
Oury, C, Servais, L, Bouznad, N et al. MicroRNAs in valvular heart diseases: potential role as markers and actors of valvular and cardiac remodeling. Int J Mol Sci 2016; 17: 1120. DOI: 10.3390/ijms17071120.CrossRefGoogle ScholarPubMed
Dai, L, Zhang, X, Hu, X et al. Silencing of microRNA-101 prevents IL-1β-induced extracellular matrix degradation in chondrocytes. Arthritis Res Ther 2012; 14: R268. DOI: 10.1186/ar4114.CrossRefGoogle ScholarPubMed
Chen, C, Ponnusamy, M, Liu, C et al. MicroRNA as a therapeutic target in cardiac remodeling. Biomed Res Int 2017; 2017: 1–25. DOI: 10.1155/2017/1278436.Google ScholarPubMed
Sayed, D, Abdellatif, M. MicroRNAs in development and disease. Physiol Rev 2011; 91: 827–887. DOI: 10.1152/physrev.00006.2010.CrossRefGoogle ScholarPubMed
Wang, G, Rao, N, Liu, D et al. Analysis of potential roles of combinatorial microRNA regulation in occurrence of valvular heart disease with atrial fibrillation based on computational evidences. PLoS One 2019; 14: e0221900. DOI: 10.1371/journal.pone.0221900.CrossRefGoogle ScholarPubMed
Wu, Y, Fan, Z, Chen, Z et al. Astragaloside IV protects human cardiomyocytes from hypoxia/reoxygenation injury by regulating miR-101a. Mol Cell Biochem 2020; 470: 41–51. DOI: 10.1007/s11010-020-03743-5.CrossRefGoogle ScholarPubMed
Ding, H, Xu, Y, Jiang, N. Upregulation of miR-101a suppresses chronic renal fibrosis by regulating KDM3A via blockade of the YAP-TGF-β-smad signaling pathway. Mol Ther - Nucleic Acids 2020; 19: 1276–1289. DOI: 10.1016/j.omtn.2020.01.002.CrossRefGoogle ScholarPubMed
Rainer, J, Meraviglia, V, Blankenburg, H et al. The arrhythmogenic cardiomyopathy-specific coding and non-coding transcriptome in human cardiac stromal cells. BMC Genomics 2018; 19: 491. DOI: 10.1186/s12864-018-4876-6.CrossRefGoogle ScholarPubMed
Yan, Y, Shi, R, Yu, X et al. Identification of atrial fibrillation-associated microRNAs in left and right atria of rheumatic mitral valve disease patients. Genes Genet Syst 2019; 94: 23–34. DOI: 10.1266/ggs.17-00043.CrossRefGoogle ScholarPubMed
Cao, S, Li, L, Li, J, Zhao, H. MiR-1299 impedes the progression of Non-small-cell lung cancer through EGFR/PI3K/AKT signaling pathway. Onco Targets Ther 2020; 13: 7493–7502. DOI: 10.2147/OTT.S250396.CrossRefGoogle ScholarPubMed
Li, W, Fang, Q, Zhong, P et al. EGFR inhibition blocks palmitic acid-induced inflammation in cardiomyocytes and prevents hyperlipidemia-induced cardiac injury in mice. Sci Rep 2016; 6: 24580. DOI: 10.1038/srep24580.CrossRefGoogle ScholarPubMed
Barrick, CJ, Roberts, RB, Rojas, M et al. Reduced EGFR causes abnormal valvular differentiation leading to calcific aortic stenosis and left ventricular hypertrophy in C57BL/6J but not 129S1/SvImJ mice. Am J Physiol Circ Physiol 2009; 297: H65–H75. DOI: 10.1152/ajpheart.00866.2008.CrossRefGoogle Scholar
Felekkis, K, Papaneophytou, C. Challenges in using circulating Micro-RNAs as biomarkers for cardiovascular diseases. Int J Mol Sci 2020; 21: 561. DOI: 10.3390/ijms21020561.CrossRefGoogle ScholarPubMed