Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure
Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure
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DOI：
10.1016/s0008-6363(00)00142-5
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发表时间：
2000-09-01
影响因子：
10.8
通讯作者：
Aukrust, P
中科院分区：
文献类型：
--
作者：
Damås, JK;Eiken, HG;Aukrust, P
目的：趋化因子调节多种生物学过程，如趋化性、胶原更新、血管生成和细胞凋亡。基于充血性心力衰竭（CHF）患者持续的免疫激活和循环中趋化因子水平的升高，我们假设趋化因子在CHF的发展中起致病作用。本研究的目的是检测人CHF中趋化因子和趋化因子受体的mRNA水平和细胞定位。研究方法：我们使用RNase保护试验和免疫组织化学技术检查了10例终末期心力衰竭患者（所有腔室）和10例器官供体的心脏。结果如下：我们的主要发现是：（i）在衰竭和非衰竭心肌中8种趋化因子和9种趋化因子受体基因的表达，（ii）在慢性衰竭和非衰竭心肌中单核细胞趋化蛋白（MCP）-1和CXC-趋化因子受体4（CXCR 4）的mRNA水平特别高，（iii）与衰竭左心房相比，在衰竭左心室中MCP-1和白细胞介素（IL）-8的mRNA水平降低，（iv）减少的趋化因子（例如，MCP-1和IL-8）和增加的趋化因子受体（例如，CCR 2、CXCR 1）mRNA水平，以及（v）MCP-1、IL-8和CXCR 4对心肌细胞的免疫定位。结论：本研究首次证明了趋化因子和趋化因子受体的基因表达和蛋白质定位在人类心肌，引入了一个新的家庭的调解员具有潜在的重要影响的心肌。在人类终末期心力衰竭中观察到的趋化因子失调可能代表了慢性心力衰竭进展中涉及的先前未知的机制。(C)2000 Elsevier Science B. V.保留所有权利。
Objectives: Chemokines regulate several biological processes, such as chemotaxis, collagen turnover, angiogenesis and apoptosis. Based on the persistent immune activation with elevated circulating levels of chemokines in patients with congestive heart failure (CHF), we have hypothesised a pathogenic role for chemokines in the development of CHF. The objective of this study was to examine mRNA levels and cellular localisation of chemokines and chemokine receptors in human CHF. Methods: We examined explanted hearts from ten patients with end-stage heart failure (all chambers) and in ten organ donors using an RNase protection assays and immunohistochemical techniques. Results: Our main findings were: (i) expression of eight chemokine and nine chemokine receptor genes in both failing and nonfailing myocardium, (ii) particularly high mRNA levels of monocyte chemoattractant protein (MCP)-1 and CXC-chemokine receptor 4 (CXCR4), in both chronic failing and nonfailing myocardium, (iii) decreased mRNA levels of MCP-I and interleukin (IL)-8 in the failing left ventricles compared to failing left atria, (iv) decreased chemokine (e.g., MCP-1 and IL-8) and increased chemokine receptor (e.g., CCR2, CXCR1) mRNA levels in failing left ventricles and failing left atria compared to corresponding chambers in the nonfailing hearts and (v) immunolocalisation of MCP-1, IL-8 and CXCR4 to cardiomyocytes. Conclusion: The present study demonstrates for the first time chemokine and chemokine receptor gene expression and protein localisation in the human myocardium, introducing a new family of mediators with potentially important effects on the myocardium. The observation of chemokine dysregulation in human end-stage heart failure may represent a previously unknown mechanism involved in progression of chronic heart failure. (C) 2000 Elsevier Science B.V. All rights reserved.