CYTOKINE GENE-EXPRESSION AFTER MYOCARDIAL-INFARCTION IN RAT HEARTS - POSSIBLE IMPLICATION IN LEFT-VENTRICULAR REMODELING

Background-A large transmural myocardial infarction may initiate struc tural and geometric changes in the left ventricle that are commonly re ferred to as remodeling. Progressive, adverse remodeling of the myocar dium may lead to ventricular dilatation and congestive heart failure. Recent studies have highlighted the effects of some cytokines on immun e-mediated myocyte injury, postischemic myocardial inflammation, and c ardiac function. However, studies of the involvement of cytokines in r emodeling of the heart are few. Methods and Results-In a rat model of myocardial infarction, progressive dilatation of the left ventricular cavity and lack of appropriate hypertrophy of the surviving myocardium were confirmed by transthoracic echocardiography. The relative expres sion of mRNA for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 in the infarcted and noninfarcted myocardium of these rats, as well as in a group of sham-operated animals, was assessed by the technique of quantitative polymerase chain reaction amplification. In the infarcted region, TNF-alpha, IL-1 beta, and IL-6 gene expressi on peaked at 1 week after infarction and decreased rapidly thereafter. In contrast, at 20 weeks after infarction, the gene expression levels of these cytokines remained significantly higher in the noninfarcted than in the infarcted zone or in the myocardium of sham-operated anima ls. Furthermore, the levels of these cytokines in the noninfarcted reg ion correlated with the left ventricular end-diastolic diameter measur ed at 8 and 20 weeks after infarction. Among these cytokines, IL-1 bet a expression was highest, and irs level correlated well with collagen deposition in the noninfarcted myocardium at 8 and 20 weeks after surg ery. At 20 weeks after infarction, immunohistochemical analysis reveal ed the presence of IL-1 beta in macrophages, endothelial cells, and va scular smooth muscle cells in the noninfarcted region, whereas no such immunoreactivity was found in the myocardium of sham-operated animals . Conclusions-These findings suggest the possible involvement of cytok ines during the remodeling process of the noninfarcted left ventricula r myocardium.