Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of heart failure after experimental myocardial infarction in rats

Abstract

An injury to the heart due to myocardial infarction (MI) may progress to heart failure. Among factors, whose interactions promote remodeling of ischemic myocardium, the increased expression of tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS) and Vascular Endothelial Growth Factor (VEGF) was found. However, little is known about the temporal and spatial relation between expression of iNOS, cytokine TNFalpha, and growth factor VEGF during pathological process of development of heart failure after the myocardial infarction. Male Sprague-Dawley rats were used for experimental myocardial infarction. The procedure was performed by anterolateral thoracotomy and snearing LAD with the metal clip. The hemodynamic measurements were done with the Langendorff preparation converted into a working heart system. The hemodynamic parameters were recorded at day 6, 11, 28, 40 and the myocardium for gene expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated rats. The VEGF, TNFalpha, iNOS, and GAPDH genes were detected by RT-PCR assay from samples taken at border zone of myocardial infarction. Expression of isoform VEGF120 was found at day 1 and 4 after MI, whereas isoforms VEGF164 and VEGF188 along with expression of TNFalpha and iNOS was found at day 1, 4, 11, 28, 40. No expression of examined genes was detected in the myocardium of control rats. The expression of studied factors was parallel with development of heart failure after myocardial infarction assessed by hemodynamic measurements. These findings confirm the postulated involvement of TNFalpha, iNOS and growth factor VEGF in the remodeling of the myocardium and development of heart failure after experimental myocardial infarction.