P209Disrupted serotonergic system in patients with pulmonary hypertension may serve as novel biomarkers new therapeutic targets and to assess severity, progression and response to treatment

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Abstract

Purpose

The role of serotonin as a factors triggering pulmonary hypertension due to left heart disease is not well identified.

Methods

In the present study, we aimed to investigate immunostaining intensity of human right auricle myocardium serotonin transporter (5-HTT) by a mouse monoclonal anti–5-HTT antibody (Advanced Targeting Systems, 1:500), as well as the concentrations of plasma and platelet serotonin (5-HT) and its metabolite - 5-hydroxyindoleacetic acid (5-HIAA) by HPLC from patients with pulmonary hypertension (PH) due to left heart disease. The control group is a people without cardiovascular diseases. Values are expressed as means ± SEM. Statistical analysis was carried out using an unpaired Mann — Whitney U-test. statistical dependence between two characteristics was carried out using Pirson correlation test. A value of p < 0.05 was considered statistically significant. All patients gave written consent for participating in the study, which was approved by the Ethical Committee.

Results

1). We established that all patients with PH (n = 14) showed significant rises of 5-HT levels in both plasma and platelets in comparison control (n = 12) (55,60 ± 10,56 (p < 0,0001), 1102,66 ± 264,11 (p < 0,01) respectively versus control 12,36 ± 1,88; 422,75 ± 120,99 nmol/L). Patients with PH have the highest plasma and platelets level of 5-HIAA in comparison control (158,98 ± 51,79 (p < 0,001); 4,23 ± 1,14 (p < 0,001) respectively versus control 24,33 ± 4,45; 1,44 ± 0,45 nmol/L). 2). We found strong positive correlation between plasma 5-HIAA and pulmonary artery pressure of PH group (r=0,6, P < 0.05); plasma 5-HT and platelets 5-HT levels (r=0,67, P < 0.05); platelets 5-HT and right ventricle size (r=0,67, P < 0.05); plasma 5-HT and right atrium size (r=0,72, P < 0.05); platelets 5-HT and right atrium size (r=0,80, P < 0.01). 3). The immunohystochemical study showed the presence of 5-HTT proteins in all studied preparations of myocardium from patients with PH due to left heart disease. Immunohistochemical staining of 5-HTT protein in myocardium from patients with PH stronger than myocardium from people without cardiovascular diseases.

Conclusions

Thus, pulmonary hypertension due to left heart disease is characterized by increased blood serotonin and 5-HIAA plasma level, increased myocardium serotonin transporter that may involved in progression of pulmonary hypertension and right ventricular failure. Changes in peripheral serotonin metabolism may be used as novel diagnostic approaches and at the same time serve as therapeutic targets.

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