Regulation of neuronal type genes in congestive heart failure rats

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Abstract
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. 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 complementary DNA (cDNA) filter arrays. Regulated genes were identified by repeated measurements and a ranked ratio analysis method. 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 = 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 alpha4 (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. These neuronal type genes may participate in underlying processes that affect contractility, intracardiac nerve function and development of arrhythmias in CHF hearts.