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 kinase C in bovine aortic endothelial cells (BAEC) as well as the induction of immediate early genes and the transcription factor activator protein-1 (AP-1) in human umbilical vein endothelial cells (HUVEC). The objective of this study was to determine whether transcriptional factor induction 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 strain. In this study, we investigated cyclic strain mediated induction of transcription factors, AP-1, cAMP response element binding protein (CRE) and nuclear factor kB (NF-kB) in cultured EC from HUVEC, human aorta (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 HUVEC, but not in BAEC. Furthermore, these findings are in marked contrast to the previously described shear stress induced activation of AP-1 and NF-kB in BAEC. There was also a temporal difference in their response 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. These results may partially explain the divergent effects of cyclic strain on EC gene expression and phenotype in EC from different vascular beds and species and underscore the difference in EC response to cyclic strain and shear stress.