Inflammation is a hallmark of several vascular diseases. The nuclear factor kappaB (NF-kappaB) transcription factors are dimeric proteins involved in the activation of a large number of genes in response to inflammato...
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Inflammation is a hallmark of several vascular diseases. The nuclear factor kappaB (NF-kappaB) transcription factors are dimeric proteins involved in the activation of a large number of genes in response to inflammatory stimuli. We report the involvement of a novel member of the ETS transcription factor, ESE-1, in mediating vascular inflammation. ESE-1 is induced in response to inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage. This induction occurs within hours of stimulation and is mediated by NF-kappaB transactivation of the ESE-1 promoter. We have identified the inducible form of nitric-oxide synthase (NOS2) as a putative target for ESE-1, ESE-1 can bind to the p50 subunit of NF-kappaB, and cotransfection of ESE-1 with the p50 and p65 subunits of NF-kappaB synergistically enhances transactivation of the NOS2 promoter by ESE-1, An ESE-1-binding site within the NOS2 promoter has been identified, the site-directed mutagenesis of which completely abolishes the ability of ESE-1 to transactivate the NOS2 promoter. Finally, in a mouse model of endotoxemia, associated with acute vascular inflammation, ESE-1 is strongly expressed in vascular endothelium and smooth muscle cells. In summary, ESE-1 represents a novel mediator of vascular inflammation.
More than a decade after its first description 1,2 , the position of endothelin-1 (ET-1) as the most potent mammalian vasoconstrictor peptide is under threat from a new 'pretender', human urotensin II (hU-II; ...
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More than a decade after its first description 1,2 , the position of endothelin-1 (ET-1) as the most potent mammalian vasoconstrictor peptide is under threat from a new 'pretender', human urotensin II (hU-II; Ref. 3). At the most recent International Conference on Endothelin (ET-6) in Montreal *, hU-II was shown to be at least ten times more potent as a vasoconstrictor than ET-1, at least in arterial tissue (S.A. Douglas, SmithKline Beecham, King of Prussia, PA, USA). However, all is not lost for ET-1 because clinical studies confirm the importance of ET-1 in the regulation of vascular tone in health and in cardiovascular disease, and preclinical studies reveal the increasingly divergent roles of ET-1 as a mediator in many new areas, including inflammation, nociception and arrhythmogenesis.
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