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

Signe Emilie Cremer; Nora Elisabeth Zois; S. G.  Moesgaard; Nathja Ravn; Susanna Cirera Salicio; J. L. Honge; Morten Holdgaard Smerup; J. Michael Hasenkam; E. Sloth; Páll S. Leifsson; Bo Torkel Falk; M. A. Oyama; C. Orton; Torben Martinussen; Lisbeth Høier Olsen

doi:10.1016/j.tvjl.2014.12.016

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

Signe Emilie Cremer, Nora Elisabeth Zois, S. G. Moesgaard, Nathja Ravn, Susanna Cirera Salicio, J. L. Honge, Morten Holdgaard Smerup, J. Michael Hasenkam, E. Sloth, Páll S. Leifsson, Bo Torkel Falk, M. A. Oyama, C. Orton, Torben Martinussen, Lisbeth Høier Olsen

9 Citations (Scopus)

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_2AR and 5-HT_2BR-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_1BR, 5-HT_2AR, 5-HT_2BR, 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_2BR 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_2BR (P = 0.02) and decreased for SERT (P = 0.03) in sMR vs. CON. There were no group differences in 5-HT_2BR 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_1BR 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_2BR and SERT, and left ventricular 5-HT_1BR in some pigs.

Original language	English
Journal	The Veterinary Journal
Volume	203
Issue number	2
Pages (from-to)	192-198
Number of pages	7
ISSN	1090-0233
DOIs	https://doi.org/10.1016/j.tvjl.2014.12.016
Publication status	Published - 1 Feb 2015

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Cremer, S. E., Zois, N. E., Moesgaard, S. G., Ravn, N., Cirera Salicio, S., Honge, J. L., Smerup, M. H., Hasenkam, J. M., Sloth, E., Leifsson, P. S., Falk, B. T., Oyama, M. A., Orton, C., Martinussen, T., & Olsen, L. H. (2015). Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation. The Veterinary Journal, 203(2), 192-198. https://doi.org/10.1016/j.tvjl.2014.12.016

Cremer, SE , Zois, NE, Moesgaard, SG, Ravn, N, Cirera Salicio, S, Honge, JL, Smerup, MH, Hasenkam, JM, Sloth, E, Leifsson, PS, Falk, BT, Oyama, MA, Orton, C, Martinussen, T & Olsen, LH 2015, 'Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation', The Veterinary Journal, vol. 203, no. 2, pp. 192-198. https://doi.org/10.1016/j.tvjl.2014.12.016

@article{f6032911301c43a6adea9b02381d1e07,

title = "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-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, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). 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 (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-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) 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 (P = 0.01). 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.",

author = "Cremer, {Signe Emilie} and Zois, {Nora Elisabeth} and Moesgaard, {S. G.} and Nathja Ravn and {Cirera Salicio}, Susanna and Honge, {J. L.} and Smerup, {Morten Holdgaard} and Hasenkam, {J. Michael} and E. Sloth and Leifsson, {P{\'a}ll S.} and Falk, {Bo Torkel} and Oyama, {M. A.} and C. Orton and Torben Martinussen and Olsen, {Lisbeth H{\o}ier}",

year = "2015",

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doi = "10.1016/j.tvjl.2014.12.016",

language = "English",

volume = "203",

pages = "192--198",

journal = "The Veterinary Journal",

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T1 - Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation

AU - Cremer, Signe Emilie

AU - Zois, Nora Elisabeth

AU - Moesgaard, S. G.

AU - Ravn, Nathja

AU - Cirera Salicio, Susanna

AU - Honge, J. L.

AU - Smerup, Morten Holdgaard

AU - Hasenkam, J. Michael

AU - Sloth, E.

AU - Leifsson, Páll S.

AU - Falk, Bo Torkel

AU - Oyama, M. A.

AU - Orton, C.

AU - Martinussen, Torben

AU - Olsen, Lisbeth Høier

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). 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 (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-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) 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 (P = 0.01). 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.

AB - 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, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). 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 (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-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) 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 (P = 0.01). 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.

U2 - 10.1016/j.tvjl.2014.12.016

DO - 10.1016/j.tvjl.2014.12.016

M3 - Journal article

C2 - 25599900

SN - 1090-0233

VL - 203

SP - 192

EP - 198

JO - The Veterinary Journal

JF - The Veterinary Journal

IS - 2

ER -

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

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