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

An injury to the heart due to myocardial infarction (MI) may progress to he art failure. Among factors, whose interactions promote remodeling of ischem ic myocardium, the increased expression of tumor necrosis factor alpha (TNF alpha), inducible nitric oxide synthase (iNOS) and Vascular Endothelial Gr owth Factor (VEGF) was found. However, little is known about the temporal a nd spatial relation between expression of iNOS, cytokine TNF alpha, and gro wth factor VEGF during pathological process of development of heart failure after the myocardial infarction. Male Sprague-Dawley rats were used for ex perimental myocardial infarction. The procedure was performed by anterolate ral thoracotomy and snearing LAD with the metal clip. The hemodynamic measu rements were done with the Langendorff preparation converted into a working heart system. The hemodynamic parameters were recorded at day 6, 11, 28, 4 0 and the myocardium for gene expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated rats. The VEGF, TNF alpha, iNOS, and G APDH genes were detected by RT-PCR assay from samples taken at border zone of myocardial infarction. Expression of isoform VEGF(120), was found at day 1 and 4 after MI, whereas isoforms VEGF(164) and VEGF(188) along with expr ession of TNF alpha and iNOS was found at day 1, 4, 11, 28, 40. No expressi on of examined genes was detected in the myocardium of control rats. The ex pression of studied factors was parallel with development of heart failure after myocardial infarction assessed by hemodynamic measurements. These fin dings confirm the postulated involvement of TNF alpha, iNOS and growth fact or VEGF in the remodeling of the myocardium and development of heart failur e after experimental myocardial infarction.