Increased release of serotonin from rat primary isolated adult cardiac myofibroblasts

Emiri Tarbit,Indu Singh,Jason Nigel Peart,Svetlana Bivol,Roselyn Barbara Rose’Meyer

doi:10.1038/s41598-021-99632-y

Abstract

Elevated blood serotonin levels have been observed in patients with heart failure and serotonin has a role in pathological cardiac function. The serotonin receptor system was examined in adult rat isolated cardiac fibroblast and myofibroblast cells. This is one of the first studies that has investigated serotonin receptors and other proteins involved in the serotonin receptor system in rat cardiac fibroblast and myofibroblast cells. Rat primary cardiac fibroblasts were isolated and transformed into myofibroblasts using 5 ng/ml TGF-β1. Transformation of cells to myofibroblasts was confirmed with the presence of α-smooth muscle actin using Western blot. Serotonin metabolism and receptor protein expression was assessed using Western blot techniques and serotonin levels measured using ELISA. The 5-HT1A, 5-HT2A and 5-HT2B receptors were found to be present in both rat cardiac fibroblasts and myofibroblast cells, however no significance in protein expression between the two cell types was found (P > 0.05). In this study a significant increase in the serotonin transporter (SERT), tryptophan hydroxylase 1 and extracellular serotonin levels was observed in rat cardiac myofibroblasts when compared to fibroblasts (P < 0.05). These results suggest that serotonin levels may rise in parallel with cardiac myofibroblast populations and contribute to the pathogenesis of heart failure via serotonin receptors.

Highlights

Suggests that the serotonin 5-HT1A receptor may have a role in serotonin mediated heart valve d isease[8]
This study aims to look at the protein expression of serotonin receptors and other important proteins associated with serotonin metabolism including the serotonin transporter (SERT), tryptophan hydroxylase (TPH1) and monoamine oxidase (MAO-A) to measure any differences in rat cardiac fibroblast and myofibroblast cells
The protein expression of key serotonin molecules associated with serotonin metabolism including MAO-A, Tryptophan Hydroxylase 1 and SERT were examined in rat cardiac fibroblasts and myofibroblasts as well the protein expression of serotonin 5 HT1A, 5HT2A and 5 HT2B receptor subtypes

Summary

Introduction

Suggests that the serotonin 5-HT1A receptor may have a role in serotonin mediated heart valve d isease[8]. There is no information related to serotonin 5-HT1A receptors in cardiac fibroblast/myofibroblast cells. The serotonin 5-HT2A receptor was examined in rat cardiac fibroblast and myofibroblast cells. The serotonin 5-HT2A receptor was reported to be expressed in both cardiac myocytes and fibroblast cells[3]. This work indicates that the serotonin 5-HT2A receptor may exert an important role in the transformation of fibroblasts to myofibroblasts. This study aims to look at the protein expression of serotonin receptors and other important proteins associated with serotonin metabolism including the serotonin transporter (SERT), tryptophan hydroxylase (TPH1) and monoamine oxidase (MAO-A) to measure any differences in rat cardiac fibroblast and myofibroblast cells. The hypothesis of this study is that serotonin receptors and serotonin system related proteins are expressed on cardiac fibroblast and myofibroblast cells. It is hypothesized that the 5-HT1A, 5-HT2A and 5-HT2B receptors will be present on both the cardiac fibroblast and myofibroblast cells

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