Development of innovative molecular technologies for the diagnosis and effectiveness of the treatment of pulmonary arterial hypertension in preschool children

AP14871767

Objective: To develop innovative molecular technologies for diagnosing and evaluating the effectiveness of treating pulmonary arterial hypertension in preschool children

Relevance

According to the International Pulmonary Hypertension (PH) Registry, 88% of reported cases of PH in children are pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD)

The relevance of this problem is determined not only by high mortality among newborns, but also by a high level of disability in subsequent periods of children's lives, which dictates the need for early diagnosis of PAH and timely surgical correction in this pathology

At the present stage, both diagnosis and differential diagnosis of pulmonary arterial hypertension in children with CHD is not possible without the use of special research methods. Along with such methods as echocardiography, chest x-ray, right heart catheterization, which are used to reliably confirm PH in children, early markers of the development of pulmonary arterial hypertension are required in the work of the clinician

Expected results:

Innovative molecular technologies for clinical and laboratory diagnostics will be developed based on the determination in the blood of children with CHD of indicators of the serotonin system involved in the pathogenesis of PAH: serotonin, its metabolite 5-HIAA, serotonin membrane transporter, serotonin 5-HT2a receptors.

  1. Mindubayeva F. – scientific supervisor of the project, Doctor of Medical Sciences, Professor of the Department of Physiology of «KMU» ; NCJSC.H-index : Scopus –3
  2. Tukbekova B. - Doctor of Medical Sciences, Professor, Head of the Department of Pediatrics and Neonatology of «KMU» ; NCJSC.H-index – 1ORCID ID 0000-0002-9115-8510
  3. Akhmaltdinova L. - Candidate of Medical Sciences, Associate Professor, Institute of Life Sciences of «KMU» ; NCJSC.H-index: Scopus – 4 Author ID в Scopus 56285614700 ORCID ID 0000-0001-5602-6136 Researcher ID in Publons B-8152-2018
  4. Bolatbekuly Zh. - Candidate of Medical Sciences, head of the children s cardiac surgery department of the Municipal State Enterprise "Multiprofile Hospital No. 2 of Karaganda".»
  5. Salikhova Y. Candidate of Medical Sciences, Associate Professor of the Department of Physiology of «KMU» ; NCJSC.H-index: Scopus – 1 Scopus Author ID: 57214714647 ORCID ID 0000-0001-8692-2425
  6. Niyazova Y. - ass. professor of the Department of Physiology of «KMU» ; NCJSC.H-index: Scopus – 1 Scopus Author ID: 57191076751ORCID ID 0000-0002-6609-330
  7. Akhmetova M. - ass. professor of the Department Physiology of of«KMU» ; NCJSC.ORCID ID 0000-0001-8357-360
  8. Ospanova M. - 3rd year PhD student of «KMU» ; NCJSC.ORCID ID 0000-0002-5247-3921
  9. Avdienko O. - junior researcher of research laboratory of Institute of Life Sciences of «KMU» ; NCJSC.H-index: Scopus – 1 ORCID ID 0000-0001-9122-1279
  10. Akzhanov G. – junior researcher, resident of the children s cardiac surgery department of the Municipal State Enterprise Multiprofile Hospital No. 2 of Karaganda .ORCID ID 0000-0001-9352-8725

The parameters of the serotonin system in children with congenital heart disease complicated by PAH were studied before and after surgical correction: the number of platelets in the blood and their characteristics (average platelet volume, coefficient of variation of platelets by volume, thrombocrit), concentration of serotonin in blood plasma and platelets, serotonin metabolite 5 -hydroxyindoleacetic acid (5-HIAA) in blood plasma, urine and platelets; the serotonin transporter SERT in platelets and the level of 5-HT2A receptors for serototonin in platelets. A statistical analysis of the obtained data was carried out. Serotonin concentration in platelets was three times higher in children with PAH compared to the control group. In patients with severe PAH, serotonin concentration decreased by 20% after surgical treatment, suggesting serotonin s role in PAH development and pulmonary vessel remodeling. Urine tests for 5-hydroxyindoleacetic acid (5-HIAA) showed a 20-fold increase in patients with CHD, which decreased after surgical treatment. Regression analysis revealed a significant correlation between plasma 5-HIAA levels and estimated mean pulmonary arterial pressure. The study demonstrated that serotonin transporter (SERT) was significantly increased in platelets of children with CHD and decreased after surgical correction. Correlation analysis revealed significant relationships between SERT, 5-HT2A, and 5-HIAA levels in platelets, indicating the involvement of the serotonin system in PAH development.

Based on the results obtained:Scientific supervisor Mindubayeva F.A. at the XXIV Congress of the Physiological Society named after. I.P. Pavlova (September 11-15, 2023, St. Petersburg) participated with a report on the topic “The influence of excess serotonin in the embryonic period of ontogenesis on the activity of the membrane serotonin transporter in early postnatal ontogenesis.”

Scientific supervisor of the project Mindubaeva F.A. and PhD student Ospanova M.D. took part in the 34th European Pediatrics Conference (Zurich, Switzerland, October 9-10, 2023) with the presentation “Study of serotonin metabolism in children with congenital heart defects.”

Target consumers are first of all, parents of children with CHD, who, already at the initial pilot stage of the application of this technology, will be ready to conduct an examination through private clinical diagnostic centers The proposed diagnostic method can be introduced into the standards for examining preschool children and will be in demand in clinical diagnostic centers.
Main publications on the project topic:
  1. Bilalova D., Mindubaуeva F., Nigmatullina R., Salikhova Y. Monocrotaline model of pulmonary hypertension in immature rats from the perspective of serotonergic regulation // Research Journal of Pharmacy and Technology. – 2023. - Vol: 16, Issue: 9 (Q2, процентиль 56).
  2. Akhmetova M., Nigmatullina R., Mindubayeva F., Tykezhanova G., Niyazova Y., Lepesbayeva G. Features of the effect of serotonin on the inotropic function of the right ventricular myocardium in the early postnatal period in infant rats with altered serotonin levels during their embryogenesis // Research Journal of Pharmacy and Technology - 2022. - Vol. 15, N 1. – P.122-126. DOI: 10.52711/0974-360X.2022.00020
  3. AAkhmetova M., Nigmatullina R., Mindubayeva F., Tykezhanova G. The effect of adrenaline on the contractility of the right ventricular myocardium in rat pups with altered serotonin concentration in ontogenesis // RJPT. - India, 2022. - №15 (5) – P. 1-7. DOI: 10.52711/0974-360X.2022.00333
  4. Mindubayeva F.A., Niyazova Yu.I., Ospanova M.D., Nigmatullina R.R. Study of serotonin metabolism in the development of pulmonary arterial hypertension in children with congenital heart defects // Abstract in the materials of the X anniversary congress “Pulmonary hypertension - 2022”: Russia, Moscow, December 5-6, 2022.
  5. Mindubayeva F.A., Nigmatullina R.R., Ospanova M.D., Akhmetova M.Zh., Niyazova Yu.I. Galembikova A.R. The influence of excess serotonin in the embryonic period of ontogenesis on the activity of the membrane serotonin transporter in early postnatal ontogenesis // Abstract in the materials of the XXIV Congress of the Physiological Society named after. I.P. Pavlov: Russia, Saint-Petersburg, September 11-15, 2023
  6. Mindubaуeva F.A., Ospanova M.D., Akhmaltdinova L.L., Bolatbekuly Zh. Study of serotonin metabolism in children with congenital heart defects // 34th European Pediatrics Conference: Zurich, Switzerland, October 9-10, 2023
  7. Ospanova M.D., Mindubayeva F.A., Sadykova D.I. Involvement of the serotonin system in the development of pulmonary arterial hypertension // Science and Health. – 2023. - No5 (T.25). Accepted for publication