The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy

The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy
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DOI:
10.1016/j.tvjl.2013
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发表时间:
2014-03-01
期刊:
影响因子:
2.2
通讯作者:
Kipar, Anja
Kipar, Anja
中科院分区:
农林科学2区
文献类型:
--
作者:
Fonfara, Sonja;Hetzel, Udo;Kipar, Anja

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心脏中的5-羟色胺信号传导由受体亚型2B(5-HTR 2B)介导。5-羟色胺对瓣膜病的作用已有报道,但5-HTR 2B在犬扩张型心肌病(DCM)中的心肌表达及其作用尚不清楚。本研究的目的是研究心肌5-HTR 2B mRNA表达在犬扩张型心肌病,并与炎症和重塑的标志物的表达结果。采用定量PCR(qPCR)研究了8只健康犬、4只DCM犬、5只DCM以外的心脏病犬和6只全身性非心脏病犬的心肌样品的5-HTR 2B mRNA表达。将结果与所选细胞因子、基质金属蛋白酶(MMP)和基质金属蛋白酶组织抑制剂(TIMP)的mRNA表达进行比较。采用激光显微切割、qPCR和免疫组织化学方法检测心肌组织中5-HTR 2B的表达,对照组心肌组织中5-HTR 2B mRNA呈组成性表达。在患有DCM的狗中,5-HTR 2B mRNA值显著大于所有其他组,在左心室和右心房中表达水平最高。心肌细胞被鉴定为5-HTR 2B mRNA和蛋白的来源。5-HTR 2B mRNA与多种细胞因子、MMPs和TIMPs的表达呈显著正相关。研究结果表明,5-羟色胺可能在正常的心脏结构和功能中发挥作用,并可能有助于DCM犬的心肌重塑和功能损害。(C)2013爱思唯尔有限公司保留所有权利。
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. (C) 2013 Elsevier Ltd. All rights reserved.