NFATC1 GENE EXPRESSION IN CHILDREN WITH BICUSPID AORTIC VALVE OF THE HEART IN DEPENDENCE ON VALVULAR FIBROSIS EXISTENCE
DOI:
https://doi.org/10.11603/1811-2471.2019.v.i3.10401Keywords:
bicuspid aortic valve, children, leaflets fibrosis, NFATC1 gene expression, calcium, cellular immunityAbstract
SUMMARY. Bicuspid aortic valve (BAV) is a common congenital heart disease leading to development of the serious heart complications. There is information about the protective role of immune system cells in development of myocardial fibrotic processes. The genes of the nuclear factor activated T-cells family (NFATC) regulating transcriptional reactions by activating the Ca-dependent calcineurin pathway and involves in both valvulogenesis and the immune response.
Material and Methods. In 40 children with BAV 18 of whom had fibrosis of the aortic valve leaflets, the parameters of blood flow on the valve, the diameter of the aortic root (Ao), the ventricular septum depth (VSd) and the left ventricle posterior wall depth (LVPWd), NFATC1 expression level (expNFATC1) by RNA extraction, the absolute and relative values of CD95+ apoptosis regulatory and CD25+ activated interleukin-2 receptor-bearing subpopulation of lymphocytes by monoclonal antibodies as well as serum calcium level (Ca) were detected.
Results. In children with BAV in valve leaflets fibrosis existence there are significant increase in expNFATC1, an increase in Ao, Ca, absolute CD25+ values, and decrease in the absolute and relative values of CD95+ lymphocyte subpopulations were found. Direct correlations were established between expNFATC1 and Ca, the absolute values of CD25+ and CD95+ T cells that is indicating an important diagnostic role of expNFATC1 in the development of valve fibrosis in this category of patients.
References
Pedersen, M.W., Groth, K.A, Mortensen, K.H., Brodersen, J., Gravholt, C.H., & Andersen, N.H. (2018). Clinical and pathophysiological aspects of bicuspid aortic valve disease. Cardiology in the Young, 29 (1), 1-10.
Sharykin, A.S. (2016). Dvustvorchatyy aortalnyy klapan u detey: Malaya anomaliya ili seryoznyy porok serdtsa? [Bicuspid aortic valve. Minor anomaly or the serious hart defect?] Consilium Medicum. Pediatriia (Pril.) – Consilium Medicum. Pediatrics (Apl.), 3, 99-102 [in Russian].
Girdauskas, E., & Borger, M.A (2013). Bicuspid aortic valve and associated aortopathy: an update. Semin. Thorac. Cardiovasc. Surg., 25 (4), 310-316. DOI: https://doi.org/10.1053/j.semtcvs.2014.01.004
Mart, C.R, & McNerny, B.E. (2013) Shape of the dilated aorta in children with bicuspid aortic valve. Ann. Pediatr. Cardiol., 6, 126-131.
Zarate, Y.A., Sellars, E., Lepard, T., Carlo, W.F., Tang X., & Collins R.T. (2015). Aortic dilation in pediatric patients. Eur. J. Pediatr., 174, 1585-1592. DOI: https://doi.org/10.1007/s00431-015-2575-8
Niaz, T., Poterucha, J.T., Johnson, J.N., Craviari, C., Nienaber, T., & Palfreeman, J. (2017). Incidence, morphology, and progression of bicuspid aortic valve in pediatric and young adult subjects with coexisting congenital heart defects. Congenit. Heart Dis., 12, 261-269. DOI: https://doi.org/10.1111/chd.12429
Tripathi, A., Wang, Y., & Jerell, J.M. (2018). Population based treated prevalence, risk factors, and outcomes of bicuspid aortic valve in a pediatric Medicaid cohort. Annals of Pediatric Cardiology, 11(2), 119-124. DOI: https://doi.org/10.4103/apc.APC_137_17
Bingruo, Wu., Baldwin, H.S, & Zhou, B. (2013). Nfatc1 directs the endocardial progenitor cells to make heart valve primordium. Trends in Cardiovascular Medicine, 23, 8, 294-300.
Khameneh, H.J., Ho, A.W., Spreafico R., Derks, H., Quek, H.Q, & Mortellaro, A. (2017). The Syk-NFAT-IL-2 pathway in dendritic cells is required for optimal sterile immunity elicited by alum adjuvants. J. Immunol., 198, 196-204. DOI: https://doi.org/10.4049/jimmunol.1600420
Bansal, S.S, Goel, M., Zhou, G., Rokosh, G., Hamid, T., & Prabhu, S.D. (2019). Dysfunctional and proinflammatory regulatory T-Lymphocytes are essential for adverse cardiac remodeling in ischemic cardiomyopathy. Circulation, 139 (2), 206-221. DOI: https://doi.org/10.1161/CIRCULATIONAHA.118.036065
Horban, N.Ye., Zadorozhna, T.D., Vovk, I.B, & Zhulkevych, I.V. (2019). Morphological features of uterine polyps in females of reproductive age. Visnyk naukovykch doslidzhnen – Bulletin Scientific Research, 2, 47-52.
Ren, X., Zhang, M., Liu, K., Hou, Z., Gao, Y., Yin, W. & Lu, B. (2016). The significance of aortic valve calcification in patients with bicuspid aortic valve disease. Int. J. Cardiovasc. Imaging, 32 (3), 471-478. DOI: https://doi.org/10.1007/s10554-015-0783-y
Signatures Selectively Activate Different NFAT Transcription Factor Isoforms, Mol. Cell, 58, 232-243. DOI: https://doi.org/10.1016/j.molcel.2015.02.027
Kamenshchyk, A.V., & Ivanko O.G. (2017). Myocardial hypertrophy and intracardial hemodynamics in children with bicuspid aortic valve. Patolohiia – Pathology, 14, 2 (40), 172-176. DOI: https://doi.org/10.14739/2310-1237.2017.2.109296
Kamenshchyk, A.V., Kamyshnyi, A.M., & Ivanko, O.H. (2016). Ekspresiia heniv nuklearnoho faktoru aktyvovanykh T-klityn u ditei z dvostulkovym aortalnym klapanom sertsia [Gene expression of nuclear factor of activated T-cells in children with bicuspid aortic valve]. Medychni perspektyvy – Medical Perspectives, 21, 3, 29-34 [in Ukrainian].
Cardona, Ye,J., Llovera, M., Comella, J.X., & Sanchis, D. (2012). Translation of myocyte enhancer factor-2 is induced by hypertrophic stimuli in cardiomyocytes through a calcineurin-dependent pathway. J. Mol. Cell. Cardiol, 53, 578-587. DOI: https://doi.org/10.1016/j.yjmcc.2012.07.013
