Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation.

Abstract Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT 1B receptor (R), 5-HT 2A R and 5-HT 2B R -induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n  = 12), mild MR (mMR, n  = 10) and severe MR (sMR, n  = 6). The gene expression levels of 5-HT 1B R, 5-HT 2A R, 5-HT 2B R, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left ventricle (LV). MV 5-HT 2B R was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV ( P  0.01). In contrast, SERT and TPH-1 were up-regulated in AP and LV compared to MV ( P  0.05). In MV, mRNA levels were increased for 5-HT 2B R ( P  = 0.02) and decreased for SERT ( P  = 0.03) in sMR vs. CON. There were no group differences in 5-HT 2B R staining (IHC) but co-localisation was found with α-SMA-positive cells in 91% of all valves and with 33% of histological lesions. In LV, 5-HT 1B R mRNA levels were increased in sMR vs. CON ( P  = 0.01). In conclusion, these data suggest that MR may affect mRNA expression of valvular 5-HT 2B R and SERT , and left ventricular 5-HT 1B R in some pigs.