The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy.
Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM.
Veterinary Pathology, Faculty of Veterinary Medicine, P.O. Box 66, 00014 University of Helsinki, Finland. Electronic address: sonjafonfara@googlemail.com.
Sonja
S
Fonfara
Veterinary Pathology, Faculty of Veterinary Medicine, P.O. Box 66, 00014 University of Helsinki, Finland.
Udo
U
Hetzel
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancy St, Philadelphia, PA 19104, USA.
Mark A
MA
Oyama
Veterinary Pathology, Faculty of Veterinary Medicine, P.O. Box 66, 00014 University of Helsinki, Finland; Veterinary Pathology, School of Veterinary Science and Department of Infection Biology, Institute of Global Health, University of Liverpool, Leahurst Campus, Neston CH64 7TE, UK.
Anja
A
Kipar
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000662:veterinary*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000235:genetics* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D044403:Receptor, Serotonin, 5-HT2B; D019715:Tissue Inhibitor of Metalloproteinase-1; D045726:Metalloproteases
Cardiac disease; Dilated cardiomyopathy; Heart failure; Myocardial remodelling; Serotonin