DECLINE OF SHEAR STRESS-INDUCED ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED KINASES, BUT NOT STRESS-ACTIVATED PROTEIN-KINASES, IN IN-VITROPROPAGATED ENDOTHELIAL-CELLS

We investigated the involvement of mitogen-activated protein kinase (M APK) signal transduction pathways in human endothelial cells in respon se to shear stress and alterations of these kinases in in vitro-propag ated endothelial cells (ECs). Potent activation (10-fold) of extracell ular signal-regulated kinase (ERK2), a member of the MAPK family, occu rred within 10 min of shear stress (5 dynes/cm(2)), whereupon rapid in activation ensued. Shear stress also induced activation of stress-acti vated protein kinase (SAPK) or c-Jun NH2-terminal protein kinase (JNK) in ECs. Suramin pretreatment completely inhibited shear stress stimul ation of ERK2, but not SAPK/JNK, highlighting a role for growth factor receptors in ERK activation. Translocation of ERK, from the cytoplasm to the nucleus was observed in shear-stressed endothelial cells. In a ddition, Eve compared activities of MAPKs in shear-stressed cells deri ved from passages ii and 10 (older). The magnitude of ERK2 activation was significantly lower in aged ECs compared to those of passage 4, wh ile SAPK/JNK was not altered in the in vitro aged ECs. A similar level of ERK2 activation was found in both young and older cells stimulated with phorbol-12-myristate-13-acetate (PMA), indicating an age-related alteration of the plasma membrane. Taken together, these findings sug gest that MAP kinase activation may be crucial for the expression of m any genes in ECs stimulated by shear stress, and that an alteration in MAPK activities could contribute to the age-related decline in prolif erative capacity. (C) 1998 Elsevier Science Inc.