HYPERTHERMIA INDUCES EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-S IN RAT CARDIAC-CELLS IN-VITRO AND IN-VIVO

Hyperthermia causes changes in expression of TGF-beta mRNA and protein in cultured cardiac cells, as well as in the heart in vivo. 12 h afte r hyperthermia, primary cultures of neonatal rat cardiomyocytes show a two- to threefold decreased expression of TGF-beta mRNAs which return s to control levels by 48 h after heat shock. In cultures of cardiac f ibroblasts, expression of TGF-beta mRNAs increases 5-25-fold, 12-48 h after heat shock, while fetal bovine heart endothelial cells show litt le change in TGF-beta expression after hyperthermia. In each case, mRN As for TGF-betas 1, 2, and 3 are regulated similarly. Hearts isolated from rats exposed to hyperthermia show an initial 20-fold decrease in TGF-beta 1 and 3 mRNA levels which return to control levels by 24 h an d subsequently are elevated two- to threefold above normal 48-72 h aft er heat shock; there is little change in TGF-beta2 mRNA. Expression of immunoreactive TGF-beta1 and 3 protein, localized intracellularly in myocytes, follows the same pattern as the mRNA expression. By 72 h, so me myocytes show hyperstaining for TGF-beta1. Staining for extracellul ar TGF-beta1/3 exhibits the opposite time course, being most intense 3 -6 h after heat shock and returning to control levels by 48 h. The inc rease in TGF-betas after hyperthermia could play a role in mediating t he reported cardioprotective effects of heat shock.