Serotonin Signaling Disruption: Technological Advances in Detecting its Role in Pediatric Pulmonary Hypertension associated with Congenital Heart Defects

Abstract

Background. Pulmonary arterial hypertension (PAH) remains a significant medical challenge with a poor prognosis. Serotonin's role in vascular regulation and its impact on pulmonary arteries, especially in children with congenital heart defects (CHD), highlight its potential importance in developing new diagnostic and treatment approaches. Aim: to study the serotonin metabolism in children with congenital heart defects, complicated with pulmonary arterial hypertension. Results: 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. Conclusions. The study underscores the growing interest in serotonin metabolism concerning PAH. Clinical data consistently link serotonin to PAH severity, with notable changes observed in urine and plasma levels of serotonin and its metabolites in affected individuals. Further research is needed to unlock the full potential of serotonin as an early biomarker and to explore innovative diagnostic and treatment strategies for PAH, ultimately improving patient outcomes and reducing complications.