VASCULAR CELL-INTERACTIONS MODULATE THE EXPRESSION OF ENDOTHELIN-1 AND PLATELET-DERIVED GROWTH-FACTOR BB

Endothelin (ET)-1 and platelet-derived growth factor (PDGF) BB are important regulators of vascular cell growth and contractile function. We tested the hypothesis that interactions between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) regulate the expression of these two factors. Bovine and rat cocultures of EC-VSMC that allowed cell contact and exchange of soluble mediators were studied. In bovine cocultures, ET-1 and PDGF B transcription decreased. Minimum levels of transcription were 39 +/- 9% of control for ET-1 and 31 +/- 6% of control for PDGF B. In contrast, steady-state mRNA levels transiently increased in coculture; maximum mRNA levels were 579 +/- 248 and 267 +/- 41% of control for ET-1 and PDGF B, respectively. ET-1 and PDGF BB protein levels were decreased in bovine cocultures. The amount of ET-1 in cocultures was 51% less and the amount of PDGF BB was 25% less than that in homotypic cultures. In rat cocultures, ET-1 protein levels were transiently increased compared with homotypic cultures; the maximum difference was 99 +/- 26%. These results indicate that EC-VSMC interactions regulate ET-1 and PDGF BB expression in EC-VSMC cocultures via multiple mechanisms. Furthermore, the interactive regulation appears to be species specific. These data suggest a novel mechanism for the regulation of these two vasoactive factors that may play an important role in cardiovascular physiology and/or pathology.