© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure
aDepartment of Cardiology, Division of Heart and Lung Diseases, The National Hospital, Oslo, Norway
bDepartment of Cardiothoracic Surgery, Division of Heart and Lung Diseases, The National Hospital, Oslo, Norway
cResearch Institute for Internal Medicine, The National Hospital, University of Oslo, Oslo, Norway
dSection of Clinical Immunology and Infectious Diseases, Medical Department, The National Hospital, Oslo, Norway
eSection of Endocrinology, Medical Department, The National Hospital, Oslo, Norway
fMSD-Cardiovascular Research Center, The National Hospital, Oslo, Norway
gInstitute for Experimental Medical Research, Ullevål Hospital, University of Oslo, Oslo, Norway
* Corresponding author. Tel.: +47-230-736-28; fax: +47-230-736-30 j.k.damas{at}klinmed.uio.no
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-1 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.
KEYWORDS Cytokines; Gene expression; Heart failure; Infection/inflammation; Monoclonal antibodies
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