کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5797602 | 1111756 | 2015 | 7 صفحه PDF | دانلود رایگان |
- The effects of mitral regurgitation (MR) on selected serotonin 5-hydroxytryptamine (5-HT) markers were evaluated in pigs.
- Haemodynamic changes associated with MR resulted in increased 5-HT2BR (R) and decreased serotonin re-uptake transporter (SERT) gene expression in mitral valves.
- MR may contribute to altered valvular 5-HT signalling and pathological valvular changes.
Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-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, nâ=â12), mild MR (mMR, nâ=â10) and severe MR (sMR, nâ=â6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, 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-HT2BR 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 (Pâ<0.01). In contrast, SERT and TPH-1 were up-regulated in AP and LV compared to MV (Pâ<0.05). In MV, mRNA levels were increased for 5-HT2BR (Pâ=â0.02) and decreased for SERT (Pâ=â0.03) in sMR vs. CON. There were no group differences in 5-HT2BR 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-HT1BR mRNA levels were increased in sMR vs. CON (Pâ=â0.01). In conclusion, these data suggest that MR may affect mRNA expression of valvular 5-HT2BR and SERT, and left ventricular 5-HT1BR in some pigs.
Journal: The Veterinary Journal - Volume 203, Issue 2, February 2015, Pages 192-198