# Peripheral Serotonergic Activation in Severe Aortic Stenosis: A Biochemical Perspective

**Authors:** Denisa Bianca Mercean, Raluca Tomoaia, Ioana Berindan-Neagoe, Liviuţa Budişan, Dana Pop, Adela Mihaela Șerban, Carmen Stanca Melincovici, Carmen Mihaela Mihu

PMC · DOI: 10.3390/ijms262110250 · 2025-10-22

## TL;DR

This study found higher levels of serotonin and its metabolite in patients with severe aortic stenosis, suggesting a possible role of the peripheral serotonergic system in the disease.

## Contribution

The study introduces a novel biochemical perspective by linking peripheral serotonergic activation to severe aortic stenosis.

## Key findings

- Serotonin levels were significantly higher in severe aortic stenosis patients compared to controls.
- 5-HIAA levels also showed significant elevation in the severe aortic stenosis group.
- Serotonin and 5-HIAA demonstrated moderate sensitivity in predicting severe aortic stenosis.

## Abstract

The involvement of the serotoninergic system in the pathogenesis of calcific aortic stenosis introduced a novel dimension to our understanding of this complex cardiovascular condition. This study aimed to assess serotonin (5-HT) and its main metabolite, 5-Hydroxyindoleacetic acid (5-HIAA) in patients with severe aortic valve stenosis (AS). The study employed a case–control design, including 76 patients who underwent transthoracic echocardiography, computed tomography (CT), and peripheral blood sampling. Serum concentrations of 5-HT and 5-HIAA were quantified using enzyme-linked immunosorbent assay (ELISA). The severe aortic valve stenosis group exhibited significantly elevated levels of 5-HT and 5-HIAA compared to the control group (5-HT 1066.5 ng/mL (IQR = 961.9–1112 ng/mL) vs. 977.4 ng/mL (IQR = 394.3–1097.9 ng/mL); p = 0.034 and 5-HIAA 57 ± 12.7 ng/mL vs. 47.5 ± 15.3 ng/mL; p = 0.004, respectively). Receiver operating characteristic (ROC) analysis revealed that 5-HT predicted severe AS with a sensitivity of 73.7% and specificity of 50% at a cut-off level > 973.5 ng/mL, whereas 5-HIAA exhibited a sensitivity of 86.8% and specificity of 47.4% when a cut-off level > 45.49 ng/mL was used. This study showed a significant elevation in the 5-HT and 5-HIAA among patients with severe AS, further supporting the potential involvement of the peripheral serotonergic system in the pathophysiology of this condition.

## Linked entities

- **Chemicals:** serotonin (PubChem CID 5202), 5-Hydroxyindoleacetic acid (PubChem CID 1826), 5-HT (PubChem CID 5202), 5-HIAA (PubChem CID 1826)
- **Diseases:** aortic stenosis (MONDO:0042981)

## Full-text entities

- **Diseases:** calcific aortic stenosis (OMIM:109730), cardiovascular condition (MESH:D002318), AS (MESH:D001024)
- **Chemicals:** 5-HT (MESH:D012701), 5-HIAA (MESH:D006897)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12610369/full.md

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Source: https://tomesphere.com/paper/PMC12610369