Hyperthermia Induces Expression

Hyperthermia causes changes in expression of TGF-ft mRNA and protein in cultured cardiac cells, as well as in the heart in vivo. 12 h after hyperthermia, primary cultures of neonatal rat cardiomyocytes show a twoto threefold decreased expression of TGF-ft mRNAs which returns to control levels by 48 h after heat shock. In cultures of cardiac fibroblasts, expression of TGF-,B mRNAs increases 5-25-fold, 12-48 h after heat shock, while fetal bovine heart endothelial cells show little change in TGF-ft expression after hyperthermia. In each case, mRNAs for TGF-,8s 1, 2, and 3 are regulated similarly. Hearts isolated from rats exposed to hyperthermia show an initial 20-fold decrease in TGF-ft 1 and 3 mRNA levels which return to control levels by 24 h and subsequently are elevated twoto threefold above normal 48-72 h after heat shock; there is little change in TGF-,f2 mRNA. Expression of immunoreactive TGF-,61 and 3 protein, localized intracellularly in myocytes, follows the same pattern as the mRNA expression. By 72 h, some myocytes show hyperstaining for TGF-#1. Staining for extracellular TGF-B1 /3 exhibits the opposite time course, being most intense 3-6 h after heat shock and returning to control levels by 48 h. The increase in TGF-,8s after hyperthermia could play a role in mediating the reported cardioprotective effects of heat shock. (J. Clin. Invest. 1993.92:404410.)