Transforming growth factor-beta regulation of endothelin expression in ratvascular cell and organ cultures

Transforming growth factor (TGF)-beta increases the production of the vasoa ctive peptide endothelin (ET) in cultures of vascular endothelial cells (EC ) and vascular smooth muscle cells (VSMC), but the physiologic or pathologi c significance of this regulation has: not been determined. The present stu dies test the hypothesis that when EC and VSMC are in direct contact or clo se proximity, ET expression is, at least in part, dependent on TGF-beta. Th e effects of TGF-beta on ET-1 mRNA (Northern analysis and reverse transcrip tion polymerase chain reaction) and peptide (radioimmunoassay) levels were assessed in rat EC and VSMC and vascular organ cultures. TGF-beta (2) (1 ng /ml) increased ET-1 mRNA in VSMC and EC plus VSMC cultures and increased ET -1 peptide in EC, VSMC, and EC plus VSMC cultures. TGF-beta (2) also increa sed ET-1 mRNA and peptide in vascular organ cultures. Antibodies that neutr alized the activities of TGF-beta (1) and TGF-beta (2) decreased ET-1 mRNA in EC plus VSMC cultures and in vascular organ cultures. These data indicat e that when EC and VSMC are in direct contact or close proximity, TGF-beta increases ET expression and active TGF-beta is present and promotes ET expr ession, These data suggest that TGF-beta is a determinant of vascular ET ex pression in vivo, and that TGF-beta regulation of ET expression would affec t cardiovascular function in health and disease.