Author(s): Mindubaуeva F., Niyazova Y., Nigmatullina R., Sadykova D., Akhmaltdinova L., Salikhova Y., Kadyrova I., Akhmetova M., Sabirova D.

Email(s): ,

DOI: 10.5958/0974-360X.2020.00436.9   

Address: Mindubaуeva F.1, Niyazova Y.1, Nigmatullina R.2, Sadykova D.2 , Akhmaltdinova L.1, Salikhova Y.1, Kadyrova I.1, Akhmetova M.1, Sabirova D.2
1“Karaganda Medical University”, NCJSC.
2Kazan State Medical University, Kazan, Russia.
*Corresponding Author

Published In:   Volume - 13,      Issue - 5,     Year - 2020

18 young children (aged from 1 month old to 2 years old) with congenital heart disease were observed. During observation they were divided into 2 groups. Group I - 8 children with CHD, not complicated by PAH. Group II 11 children with CHD, complicated by PAH. The content of serotonin and its transporter in platelets, the amount of serotonin in serum were determined. Serotonin content was determined by enzyme-linked immunosorbent assay. The study was performed using the Serotonin ELISA diagnostic kit, IBL Hamburg on the Evolis automated robotic station (BioRad). To determine the Sodium-Dependent serotonin transporter (SLC6A4) there was used the method of quantitative sandwich ELISA of Cusabio production. The main initiator of the development of PAH is development of endothelial dysfunction of the pulmonary vessels. Since the cause of this dysfunction is associated with functional disorders of the serotonergic system, our task was to determine the content of SERT and serotonin in platelets in the studied groups. We suggest that the serotonin transporter (SERT), which is responsible for the proliferation of the pulmonary artery smooth-muscle cells (PASMC), can be used as a biomarker for predicting and diagnosing PAH in children with CHD. The need for early biomarkers in the diagnosis of PAH in children is claimed by scientists from many countries of the world [1,2]. The results of our studies showed a significant increase in the concentration of SERT in platelets in group II, compared with group I more than several times. The serotonin content in platelets in children of group II tended to decrease as compared with group I. Perhaps, an excessive increase in transporters in platelets is sufficient in itself for the induction of PASMC hyperplasia and the subsequent development of PAH. It is necessary to continue research in this direction, which will help to reveal and understand the molecular mechanisms by which SERT regulates the proliferation of PASMC and the role of serotonin and its transporter in the development of PAH in children.

Cite this article:
Mindubaуeva F., Niyazova Y., Nigmatullina R., Sadykova D., Akhmaltdinova L., Salikhova Y., Kadyrova I., Akhmetova M., Sabirova D. Membrane serotonin transporter as a Biomarker of Pulmonary arterial hypertension in children with Congenital Heart Defect. Research J. Pharm. and Tech 2020; 13(5): 2435-2438. doi: 10.5958/0974-360X.2020.00436.9

Mindubaуeva F., Niyazova Y., Nigmatullina R., Sadykova D., Akhmaltdinova L., Salikhova Y., Kadyrova I., Akhmetova M., Sabirova D. Membrane serotonin transporter as a Biomarker of Pulmonary arterial hypertension in children with Congenital Heart Defect. Research J. Pharm. and Tech 2020; 13(5): 2435-2438. doi: 10.5958/0974-360X.2020.00436.9   Available on:

1.    Kelley L. Biomarkers  for pediatric  pulmonary arterial hypertension- a call to collaborate Frontiers in Pediatrics.  Pediatric  Pulmonology. 2014; 2. Article 7. doi: 10.3389 fped.2014.00007.
2.    Marius M. Difinitions and diagnosis of Pulmonary hypertension . Journal of the  American College of Cardiology. 2013; 62: 25.
3.    Avdeev S.N. Pulmonary hypertension.GEOTAR- Media. 2015; 416.
4.    Nebigil, C.G., Pharm D., Maroteaux L. Functional consequence of serotonin 5-HT2B receptor signaling in heart. Role of mitochondria in transition between hytertrophy and  heart failure.  Circulation. 2003; 108: 902-908.
5.    Cote, F. Disruption of the nonneuronal tph 1 gene demonstrates the importance of peripheral serotonin in cardiac   function/ F. Cote, E. Thevenot, C. Fligny. Proc. natl. acad. sci. USA. 2004;100: 13525-13530.
6.    Blakely RD, Berson HE, Fremeau RT, Jr, Caron MC, Peek MM, Priace HK, Bradley CC.     Cloning and expression of a functional the 5HT transporter from rat brain. Nature. 1991; 354: 66–70.
7.    Hoffman BJ, Mezey E, Browstein MJ. Cloning of the 5HT transporter affected by antidepressants. Science. 1991;254:579–580.
8.    Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996; 29:1527–1531.
9.    Ramamoorthy S, Cool DR, Mahesh VB, Leibach FH, Melikian HE, Blakely RD, Ganapathy V. Regulation of the human serotonin transporter. Cholera toxin-induced stimulation of serotonin uptake in human placental choriocarcinoma cells is accompanied by increased serotonin transporter mRNA levels and serotonin transporter-specific ligand binding. J. Biol. Chem. 1993a ;268:21626–21631.
10.    Rudnick  G. Active transport of 5-hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets. J. biol. chem. 1977; 252: 2170-2174.
11.    Nigmatullina R.R., Matveeva V.L., Chibireva M.D. The influence of selective serotonin re-uptake inhibitor fluoxetine on inotropic function of myocardium in the ontogenesis of rats. Ross FiziolZhIm I M Sechenova. 2014; 100(3): 348-359.
12.    GillisC.N., Pitt B.R. The fate of circulating amines within the pulmonary circulation. Annu rev physiol. 1982; 44: 269-281.
13.    Balkovetz D.F., Tiruppathi C., Leibach F.H. Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes. J. biol. chem. 1989; 264: 2195-2198.
14.    Zhu C.B., Hewlett W.A., Francis S.H. Stimulation of serotonin transport by the cyclic GMP phosphodiesterase-5 inhibitor sildenafil. Eur j. pharmacol. 2004; 1: 1-6.
15.    Ren W., Watts S.W., FanburgB.L.Serotonin transporter interacts with the PDGF receptor in PDGF-BB-induced signaling and mitogenesis in pulmonary artery smooth muscle.Am J Physiol Lung Cell Mol Physiol. 2011; 300: 486–497.
16.    Liu Y.,FanburgB.L.  Serotonin-induced growth of pulmonary artery smooth muscle requires activation of phosphatidylinositol 3-kinase/serinethreonine protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase 1.Am J Respir Cell Mol Biol. 2006; 34: 182–191.
17.    Walther D.J.,Peter J.U., Winter S. Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release. Cell. 2003; 115: 851–862.
18.    Guilluy C.,Eddahibi S., AgardC. RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling. Am J RespirCrit Care Med. 2009; 179: 1151–1158.
19.    Chen C.,Han X., Fan F. Serotonin drives the activation of pulmonary artery adventitial fibroblasts and TGF-þƒ1/ Smad3-mediated fibrotic responses through 5-HT2A receptors. Mol Cell Biochem. 2014; 397: 267–276.
20.    Hood K.Y., Montezano A.C., Harvey A.P. Nicotinamide adenine dinucleotide phosphate oxidase-mediated redox signaling and vascular remodeling by 16alpha-hydroxyestrone in human pulmonary artery cells: implications in pulmonary arterial hypertension. Hypertension. 2016; 68: 796–808.
21.    Guignabert C.,Izikki M.,  Tu L.I. Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res. 2006; 98: 1323–1330.
22.    Lee S.L.,Wang W.W., Moore B.J. Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture. Circ Res. 1991; 68: 1362–1368.
23.    Castro E. C. C.,Sen P., Parks W. T.,Langston C., Galambos C. The Role of Serotonin Transporter in Human Lung Development and in Neonatal Lung Disorders. Canadian Respiratory Journal. 2017. – 10 pages. - Article ID 9064046,
24.    Brenner B, Harney JT, Ahmed BA, Jeffus BC, Unal R, Mehta JL, Kilic F. Plasma serotonin level and the platelet serotonin transporter. J Neurochem. 2007;102:206–216
25.    Broer S, Gether U. The solute carrier 6 family of transporters. Br J Pharmacol. 2012;167:256–278.
26.    Kristensen AS, Andersen J, Jorgensen TN, Sorensen L, Eriksen J, Loland CJ, Stromgaard K, Gether U. SLC6 neurotransmitter transporters: structure, function, and regulation. Pharmacol Rev. 2011;63:585–640.

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