CYCLIC STRAIN CAUSES HETEROGENEOUS INDUCTION OF TRANSCRIPTION FACTORS, AP-1, CRE BINDING-PROTEIN AND NF-KB IN ENDOTHELIAL-CELLS - SPECIES AND VASCULAR BED DIVERSITY

Recent studies demonstrate that cyclic strain stimulates protein kinas e C in bovine aortic endothelial cells (BAEC) as well as the induction of immediate early genes and the transcription factor activator prote in-1 (AP-1) in human umbilical vein endothelial cells (HUVEC). The obj ective of this study was to determine whether transcriptional factor i nduction in endothelial cells (EC) exposed to strain is the same with regard to the species and vascular bed they are derived from. Evidence for a heterogeneous response for growth, orientation and prostacyclin secretion has been obtained for a variety of EC exposed to cyclic str ain. In this study, we investigated cyclic strain mediated induction o f transcription factors, AP-1, cAMP response element binding protein ( CRE) and nuclear factor kB (NF-kB) in cultured EC from HUVEC, human ao rta (HAEC), and BAEC. EC were exposed to 10% average strain at 60 cpm for up to 24 h. At varying time points, nuclear protein was extracted and analyzed for production of AP-1, CRE and NF-kB by electromobility shift assay. The results demonstrate that EC exposure to cyclic strain leads to a significant induction of AP-1, CRE and NF-kB in HAEC and H UVEC, but not in BAEC. Furthermore, these findings are in marked contr ast to the previously described shear stress induced activation of AP- 1 and NF-kB in BAEC. There was also a temporal difference in their res ponse such that stretch-induced activation of AP-1 and NF-kB peaked at 4 h, whereas CRE increased in a biphasic manner at 15 min and 24 h. T hese results may partially explain the divergent effects of cyclic str ain on EC gene expression and phenotype in EC from different vascular beds and species and underscore the difference in EC response to cycli c strain and shear stress.