CYTOKINE EXPRESSION INCREASES IN NONMYOCYTES FROM RATS WITH POSTINFARCTION HEART-FAILURE

Growing evidence suggests that cardiac nonmyocyte cells may play an im portant regulatory role in the response to myocardial overload and inj ury via altered expression of paracrine products, such as cytokines an d growth factors, but information concerning the cell-specific changes in the expression of these substances in heart-failure models is limi ted. Therefore, cardiac nonmyocytes were isolated from rats 1 day and 1 and 6 wk after left coronary artery ligation with resulting hemodyna mic evidence of heart failure and in sham-operated control animals. mR NAs for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 be ta, IL-6, transforming growth factors (TGF)-beta 1 and TGF-beta 3, and type I and type III collagen were measured by Northern analyses. The temporal and quantitative relationships between the expression of thes e cytokines and collagen and myocyte hyper trophy were determined, mRN A expression of IL-1 beta was increased by 1.3-fold at 1 day and 1 wk, and expression of TNF-alpha, IL-1 beta, IL-6, TGF-beta 1, and TGF-bet a 3 were increased by 1.4- to 2.1-fold at the l-wk time point before r eturning toward baseline at 6 wk. There were significant correlations between the expression of these cytokines and the expression of types I and III collagen, which also peaked at 1 wk. Myocyte hypertrophy was seen first at 6 wk. These observations are consistent with a hypothes is that nonmyocyte cells play a regulatory role in the extracellular m atrix changes during postinfarction remodeling and highlight the impor tance of examining cell-specific changes in gene expression and elucid ating the role of cell-to-cell interactions within the myocardium.