Blood flow that is steady and laminar is known to be atheroprotective. One likely mechanism is enhanced endothelial cell (EC) survival. Because the mitogen-activated protein kinases (MAPKs) are known regulators of cell survival, we investigated the role of Big @entity30512 (BMK1 or @entity61762 ), which is potently stimulated by fluid shear stress. To activate BMK1, we overexpressed constitutively active (CA)-MEK5 in @entity291 lung microvascular ECs (BLMECs). Cell apoptosis was induced by growth factor deprivation (0% serum for 24 hours). Analysis of cell viability with @entity98 assay showed that activation of BMK1 by CA-MEK5 significantly improved cell viability from 48% to 87% and decreased apoptotic cells from 49% to 10%. Growth factor deprivation induced caspase-3 activity 5.2-fold, which was inhibited (approximately 60%) by CA-MEK5 overexpression. In contrast, inhibiting BMK1 activity by overexpressing dominant-negative BMK1 (DN-BMK1) stimulated apoptosis in BLMECs. Steady laminar fluid shear stress inhibited BLMEC apoptosis, and this protective effect was also reduced significantly by overexpressing DN-BMK1. Analysis of antiapoptotic mechanisms showed that both shear stress and CA-MEK5 stimulated phosphorylation of @entity70431 on Ser112 and Ser136, whereas DN-BMK1 inhibited phosphorylation. Phosphorylation of @entity70431 induced by BMK1 activation was independent of Akt, PKA, or p90RSK kinase activity. These results suggest that BMK1 activation by steady laminar flow is atheroprotective by inhibiting EC apoptosis via phosphorylation of @entity70431 .

Big mitogen-activated protein kinase (BMK1)/ XXXX protects endothelial cells from apoptosis.

@entity30512 :: ('327672(Tax:9913)', 'Gene') :: ['MAPK-1'] @entity98 :: ('CHEBI:53233', 'Chemical') :: ['MTT'] @entity61762 :: ('537703(Tax:9913)', 'Gene') :: ['ERK5'] @entity291 :: ('9913', 'Species') :: ['bovine'] @entity70431 :: ('615013(Tax:9913)', 'Gene') :: ['Bad']
@entity61762 :: (537703(Tax:9913),Gene) :: ['ERK5']
