ABSTRACT
Acute (5min) stimulation with cyclic stretch or fluid shear stress, significantly increased the production of 11,12-, and 14,15-EET by cultured porcine coronary endothelial cells. Prolonged exposure (24h) to cyclic stretch or shear stress increased the expression of cytochrome P450 2C mRNA and protein by five to ten-fold, effects which were accompanied by comparable increases in EET generation. Inhibitors of tyrosine kinases and the p38 mitogenactivated protein kinase, which are activated in endothelial cells by cyclic stretch, had no influence on the stretch-induced increase in cytochrome P450 2C expression. An increase in cytochrome P450 2C mRNA and protein expression was also observed in native endothelial cells, in isolated segments of porcine coronary artery perfused under steady flow or pulsatile conditions for 6h. These results have identified the coronary cytochrome P450 2C as a novel mechano-sensitive gene product in native and cultured endothelial cells.
