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J Thorac Cardiovasc Surg 2005;129:1383-1390
© 2005 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
a Institute of Cardiovascular Research, Bayer AG, Wuppertal, Germany
b Department of Cardiothoracic Surgery, Martin Luther University, Halle-Wittenberg, Germany
d Institute of Pathophysiology, Martin Luther University, Halle-Wittenberg, Germany
c Department of Pharmacology and Toxicology, University of Technology, Dresden, Germany
e Vascular Endothelium and Microcirculation, University of Technology, Dresden, Germany
Received for publication May 7, 2004; revisions received August 23, 2004; accepted for publication August 27, 2004. * Address for reprints: Henning Morawietz, PhD, Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. (Email: Henning.Morawietz{at}mailbox.tu-dresden.de).
OBJECTIVES: The knowledge of chamber-specific gene expression in human atrial and ventricular myocardium is essential for the understanding of myocardial function and the basis for the identification of putative therapeutic targets in the treatment of cardiac arrhythmia and heart failure. In this study the gene expression pattern of human left atrial and ventricular myocardium was analyzed.
METHODS: Global mRNA expression patterns with high-density oligonucleotide arrays between left atrial and left ventricular myocardium of 6 patients with heart failure undergoing heart transplantation were compared. Clustering of microarray data confirmed chamber-specific gene expression profiles. Genes similarly expressed in all patients were further analyzed, and data were confirmed by means of real-time polymerase chain reaction and Western blot analysis.
RESULTS: Of 22,215 genes examined, 7115 transcripts were found to be expressed in all 12 human myocardial samples. One hundred twenty-five genes were differentially expressed between left atrial and left ventricular specimens in all patients examined. Novel genes preferentially expressed in human atria were identified. Interestingly, several potassium channels of subfamily K are more highly expressed in atria than in ventricles. Members of the potassium inwardly rectifying channel of subfamily J were found to be more highly expressed in human ventricular myocardium. Finally, chronic atrial fibrillation was associated with reduced atrial expression of the potassium channel TWIK-1, suggesting potential contribution of the corresponding current to electrical remodeling.
CONCLUSIONS: Human atria and ventricles show specific gene expression profiles. Our data provide the basis of a comprehensive understanding of chamber-specific gene expression in diseased human hearts and will support the identification of therapeutic targets in the treatment of arrhythmia and heart failure.
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