Hemodynamic Regulation of Tumor Necrosis Factor-α Gene and Protein Expression in Adult Feline Myocardium

Abstract Tumor necrosis factor-α (TNF-α) mRNA and protein biosynthesis were examined in adult feline myocardium in the presence and absence of superimposed hemodynamic pressure overloading. A brief period of hemodynamic pressure overloading ex vivo resulted in de novo TNF-α mRNA expression within 30 minutes and de novo TNF-α protein production within 60 minutes; neither TNF-α mRNA nor protein was detected in hearts perfused at normal perfusion pressures. Moreover, TNF-α mRNA and protein biosynthesis were observed in myocyte and nonmyocyte cell types in the pressure-overloaded hearts. To determine whether a simple passive stretch of the myocardium was a sufficient stimulus for TNF-α biosynthesis, we examined TNF-α mRNA expression in stretched and unstretched papillary muscles. This study showed that myocardial stretch was a sufficient stimulus for the induction of TNF-α mRNA biosynthesis. The functional significance of the intramyocardial production of TNF-α was determined by examining cell motion in isola...