Regulation of neuronal type genes in congestive heart failure rats K. B. Andersson, 1,2 G. Florholmen, 1,2 L. H. Winer, 1 T. Tønnessen 1,2,3 and G. Christensen 1,2 1 Institute for Experimental Medical Research, Ullevaal University Hospital, Oslo, Norway 2 Center for Heart Failure Research, University of Oslo, Oslo, Norway 3 Department of Cardiothoracic Surgery, Ullevaal University Hospital, Oslo, Norway Received 4 May 2005, revision requested 23 June 2005, revision received 17 August 2005, accepted 26 September 2005 Correspondence: K. B. Andersson, Institute for Experimental Medical Research, Ullevaal University Hospital, 0407 Oslo, Norway. E-mail: k.b.andersson@medisin.uio.no Abstract Aim: After myocardial infarction (MI), complex changes in the heart occur during progression into congestive heart failure (CHF). This study sought to identify regulated genes that could have a functional role in some of the changes seen in CHF. Methods: Myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD) in Wistar rats. Gene expression changes in 1- and 7-day MI left ventricular myocardium was analysed using comple- mentary DNA (cDNA) filter arrays. Regulated genes were identified by repeated measurements and a ranked ratio analysis method. Results: A total of 135 genes were identified as differentially expressed. A few genes were robustly regulated at 1-day MI. In 7-day CHF hearts, changes in the expression of neuronal type genes was prominent (32%, n ¼ 28). Eleven of these genes with no described association with CHF were selected for validation. One gene failed the validation. In CHF hearts, the expression of the muscarinic m4 (Chrm4) and nicotinic a4 (Chrna4) acetylcholin receptors, the ATP receptor P2rx4, nerve growth factor receptor (Ngfr), discoidin domain receptor 1 (Ddr1), neuronal pentraxin receptor (Nptxr), peripheral myelin protein Pmp-22, leukocyte type 12-lipoxygenase (Alox15), cytochrome P450 4F5 (Cyp4F5) and cardiac Kcne1 were all increased (range 1.6–6.0-fold, P < 0.01 for all genes). The lack of significant regulation of these genes at 1-day post-MI, suggests that the induction of these genes at 7-day post-MI is not a short-term response induced by the infarct itself. Conclusion: These neuronal type genes may participate in underlying pro- cesses that affect contractility, intracardiac nerve function and development of arrhythmias in CHF hearts. Keywords array analysis, heart failure, infarction, neuronal genes. Myocardial infarction (MI) is a leading cause of heart failure. The response in the heart to MI is complex and some of the key processes are hypertrophic growth, remodelling of the extracellular matrix, reactivation of cardiac foetal genes, changes in energy metabolism and electrophysiological remodelling. More than 50% of post-MI congestive heart failure (CHF) patients die because of the development of arrhythmias and sudden death (Braunwald 1997). It was early recognized that sympathetic nervous activity is increased in CHF patients, and major attention has been given to the physiological and molecular characterization of adren- ergic signalling pathways. CHF patients also have decreased parasympathetic responses (Eckberg et al. 1971). However, the molecular details of parasympa- thetic signalling is not as well characterized in the heart. Recently, it has been suggested that processes such as nerve sprouting and sympathetic hyperinnervation may Acta Physiol 2006, 186, 17–27 Ó 2006 Scandinavian Physiological Society 17