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The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy
Authors:Sonja Fonfara  Udo Hetzel  Mark A Oyama  Anja Kipar
Institution:1. CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n 4450-208 Matosinhos, Portugal;2. ICBAS - Institute of Biomedical Sciences of Abel Salazar, University of Porto, Rua De Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal;3. Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal;4. School of Marine Studies, Faculty of Science, Technology and Environment, The University of The South Pacific, Laucala Bay Road, Suva, Fiji;1. Novo Nordisk A/S, Maaloev, Denmark;2. Laboklin GmbH, Bad Kissingen, Germany;3. Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Finland;4. Din Veterinaer, Helsingborg, Sweden;5. Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark;6. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
Abstract: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.
Keywords:Serotonin  Heart failure  Cardiac disease  Dilated cardiomyopathy  Myocardial remodelling
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