Cytokine Gene Expression After Myocardial Infarction in Rat Hearts: Possible Implication in Left Ventricular Remodeling

Abstract

Background —A large transmural myocardial infarction may initiate structural and geometric changes in the left ventricle that are commonly referred to as remodeling. Progressive, adverse remodeling of the myocardium may lead to ventricular dilatation and congestive heart failure. Recent studies have highlighted the effects of some cytokines on immune-mediated myocyte injury, postischemic myocardial inflammation, and cardiac function. However, studies of the involvement of cytokines in remodeling 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 expression of mRNA for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, 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-α, IL-1β, and IL-6 gene expression 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 animals. Furthermore, the levels of these cytokines in the noninfarcted region correlated with the left ventricular end-diastolic diameter measured at 8 and 20 weeks after infarction. Among these cytokines, IL-1β expression was highest, and its level correlated well with collagen deposition in the noninfarcted myocardium at 8 and 20 weeks after surgery. At 20 weeks after infarction, immunohistochemical analysis revealed the presence of IL-1β in macrophages, endothelial cells, and vascular 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 cytokines during the remodeling process of the noninfarcted left ventricular myocardium.