Interaction in endothelium of non-muscular XXXX and the NF-kB pathway is critical to lipopolysaccharide-induced @entity455 .

@entity1 @entity650 @entity455 @entity295 @entity19077 @entity19 @entity19102 @entity409 @entity842 @entity3623 @entity130
During @entity295 , endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in @entity130 associated with oxidative and nitrative stresses, and @entity455 . The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor k-light-chain enhancer of activated B cells (NF-kB). Aortic rings from @entity19 were exposed in  vitro to LPS and, then, vascular reactivity was measured. @entity1 aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-kB was analysed. We provide evidence that nmMLCK deletion prevents @entity455 induced by in  vitro LPS treatment but not @entity409 in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-kB activation and increases @entity842 (NO) release via induction of @entity3623 ( @entity3623 ) within the vascular wall. Also, removal of endothelium prevented both NF-kB and @entity3623 expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, @entity650 accounts for the induction of @entity3623 on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-kB activation occurs via increased @entity19077 activity sensitive to the @entity19077 inhibitor, @entity19102 , and physical interactions between nmMLCK and NF-kB. We report for the first time on NF-kB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies.
