Exposure of Endothelial Cells to Cyclic Strain Induces c-fos, fosB and c-jun But not jun B or jun D and Increases the Transcription Factor AP-1

Hemodynamic forces modulate endothelial cell (EC) proliferation and gene expression but the intracellular regulatory events are unknown. Since we have shown that protein kinase C is activated in EC subjected to cyclic strain, the aim of this study was to determine if there was downstream induction of the fos and jun genes and the nuclear transciription factor activator protein-1 (AP-1). Human umbilical vein EC (HUVEC) were grown to confluence on flexible-bottomed culture plates. Vacuum (-20 kPa) was used to deform the membranes at 60 cycles/min (0.5 s strain; 0.5 s relaxation) for up to 24 h. Total RNA was extracted, elec-trophoresed and analyzed for expression of jun and fos family genes by Northern blot. In other experiments, EC were harvested, lysed, and nuclear proteins extracted and analyzed by gel shift for AP-1. The results demonstrate that exposure of HUVEC to cyclic strain leads to a significant induction of c-fos, fosB and c-jun genes by 30 min. junB and junD were not affected. AP-1 production was increased by gel shift at 2 h. Thus, the cyclic strain stimuli may be coupled to EC response via the activation of PKC and increased steady state levels of different fos and jun products, which may enhance the formation of transcriptional activator AP-1.