Thyrotoxic heart disease (THD) is a common and severe complication of hyperthyroidism and the etiology of this complication remains poorly understood. Activation of the rennin—angiotensin— aldosterone system by excess thyroxin is one of the major factors that contribute to the pathogenesis of THD. Several microRNAs such as miR-21, miR-155, miR-208a, and miR-499 are closely related to the rennin—angiotensin—aldosterone system and therefore should be involved in this process. Our study intends to explore whether these miRNAs are involved in the pathogenesis of THD, and if these miRNAs could be secreted into the circulation and serve as sentinel indicators for THD. Though there is a trend of elevation of miR- 155 in THD than in simple hyperthyroidism patients, we did not find statistically significant differences in the expression of these miRNAs in the blood of THD patients, but we found that miR-155 was significantly up-regulated in patients with Graves’ disease with or without THD in comparison with healthy controls. Thus, miR-155 can serve as a novel biomarker for Graves’ disease and can play important roles in pathogenesis of Graves’ disease.
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References
Barreto-Chaves ML, Senger N, Fevereiro M, Parletta AC, Takano A. Impact of hyperthyroidism on cardiac hypertrophy. Endocr. Connect. 2020;9(3):R59-R69. doi: https://doi.org/10.1530/EC-19-0543
Carneiro-Ramos MS, Diniz GP, Nadu AP, Almeida J, Vieira RL, Santos RA, Barreto-Chaves ML. Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation. Basic Res. Cardiol. 2010;105(3):325-335. doi: https://doi.org/10.1007/s00395-010-0089-0
Chen LY, Wang X, Qu XL, Pan LN, Wang ZY, Lu YH, Hu HY. Activation of the STAT3/microRNA-21 pathway participates in angiotensin II-induced angiogenesis. J. Cell. Physiol. 2019;234(11):19640-19654. doi: https://doi.org/10.1002/jcp.28564
Diniz GP, Lino CA, Moreno CR, Senger N, Barreto-Chaves MLM. MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone. J. Cell Physiol. 2017;232(12):3360-3368. doi: https://doi.org/10.1002/jcp.25781
Diniz GP, Takano AP, Barreto-Chaves ML. MiRNA-208a and miRNA-208b are triggered in thyroid hormone-induced cardiac hypertrophy - role of type 1 Angiotensin II receptor (AT1R) on miRNA-208a/α-MHC modulation. Mol. Cell. Endocrinol. 2013;374(1-2):117-124. doi: https://doi.org/10.1016/j.mce.2013.04.010
Li K, Du Y, Jiang BL, He JF. Increased microRNA-155 and decreased microRNA-146a may promote ocular inflammation and proliferation in Graves’ ophthalmopathy. Med. Sci. Monit. 2014;20:639-643. doi: https://doi.org/10.12659/MSM.890686
Martínez-Hernández R, Sampedro-Núñez M, Serrano-Somavilla A, Ramos-Leví AM, de la Fuente H, Triviño JC, Sanz-García A, Sánchez-Madrid F, Marazuela M. A MicroRNA Signature for Evaluation of Risk and Severity of Autoimmune Thyroid Diseases. J. Clin. Endocrinol. Metab. 2018;103(3):1139-1150. doi: https://doi.org/10.1210/jc.2017-02318
Navickas R, Gal D, Laucevičius A, Taparauskaitė A, Zdanytė M, Holvoet P. Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. Cardiovasc. Res. 2016;111(4):322-337. doi: https://doi.org/10.1093/cvr/cvw174
Otsu H, Watanabe M, Inoue N, Masutani R, Iwatani Y. Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases. Clin. Chem. Lab. Med. 2017;55(5):626-635. doi: https://doi.org/10.1515/cclm-2016-0449
Poller W, Dimmeler S, Heymans S, Zeller T, Haas J, Karakas M, Leistner DM, Jakob P, Nakagawa S, Blankenberg S, Engelhardt S, Thum T, Weber C, Meder B, Hajjar R, Landmesser U. Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives. Eur. Heart J. 2018;39(29):2704- 2716. doi: https://doi.org/10.1093/eurheartj/ehx165
Takano APC, Senger N, Munhoz CD, Barreto-Chaves MLM. AT1 receptor blockage impairs NF-κB activation mediated by thyroid hormone in cardiomyocytes. Pflugers Arch. 2018;470(3):549-558. doi: https://doi.org/10.1007/s00424-017-2088-6
Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980-984. doi: https://doi.org/10.1038/nature07511
Vargas F, Rodríguez-Gómez I, Vargas-Tendero P, Jimenez E, Montiel M. The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations. J. Endocrinol. 2012;213(1):25-36. doi: https://doi.org/10.1530/JOE-11-0349
Zhang L, Masetti G, Colucci G, Salvi M, Covelli D, Eckstein A, Kaiser U, Draman MS, Muller I, Ludgate M, Lucini L, Biscarini F. Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves’ disease and orbitopathy. Sci. Rep. 2018;8(1):8386. doi: https://doi.org/10.1038/s41598-018-26700-1
Zheng L, Xu CC, Chen WD, Shen WL, Ruan CC, Zhu LM, Zhu DL, Gao PJ. MicroRNA-155 regulates angiotensin II type 1 receptor expression and phenotypic differentiation in vascular adventitial fibroblasts. Biochem. Biophys. Res. Commun. 2010;400(4):483-488. doi: https://doi.org/10.1016/j.bbrc.2010.08.067
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 172, No. 8, pp. 148-156, August, 2021
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Li, H.M., Chen, Y.X., Fan, X.M. et al. Expression of Circulating Rennin—Angiotensin—Aldosterone-Related microRNAs in Patients with Thyrotoxic Heart Disease. Bull Exp Biol Med 172, 125–132 (2021). https://doi.org/10.1007/s10517-021-05348-4
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DOI: https://doi.org/10.1007/s10517-021-05348-4