Oleic acid induces endothelin-1 expression through activation of protein kinase C and NF-κB

This study investigated the effect of oleic acid on the expression levels of endothelin-1 (ET-1) and on the signaling pathways mediating it in human aortic endothelial cells (HAECs). ET-1 mRNA expression was significantly increased by oleic acid in a dose-and time-dependent manner. Elevation of ET-I expression in response to oleic acid was inhibited by the protein kinase C (PKC) inhibitor, GF109203X, or the NF-kappabeta inhibitor, pyrrolidine dithiocarbamate. In addition, both PKC and NF-kappabeta activities were significantly increased by oleic acid. Immunoblot analysis revealed that conventional PKCs (PKC-alpha and -betaII isoforms) were significantly increased in the membranous fractions of HAECs treated with oleic acid. PKC inhibitor completely abolished oleic acid-induced NF-kappabeta activation, suggesting that PKC activation is upstream of NF-kappabeta activation in oleic acid-induced ET-1 expression. These data suggest that elevated plasma oleic acid levels observed in obese, insulin-resistant subjects result in endothelial dysfunction, at least in part, through an increase in ET-1 expression. (C) 2003 Elsevier Science (USA). All rights reserved.