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Severe sepsis, defined as sepsis with acute organ dysfunction, is associated with high morbidity and mortality rates. The development of novel therapies for sepsis is critically dependent on an understanding of the basic mechanisms of the disease. The pathophysiology of severe sepsis involves a highly complex, integrated response that includes the(More)
Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the first of a 2-part review focused on phenotypic heterogeneity of blood vessel endothelium. This review provides an historical perspective of our understanding of endothelial heterogeneity, discusses(More)
Although tissue injury and inflammation are considered essential for the induction of angiogenesis, the molecular controls of this cascade are mostly unknown. Here we show that a macrophage-derived peptide, PR39, inhibited the ubiquitin-proteasome-dependent degradation of hypoxia-inducible factor-1alpha protein, resulting in accelerated formation of(More)
Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic(More)
NADPH oxidase has been shown to play an important role in cardiovascular biology. The goal of the present study was to determine whether NADPH oxidase activity is important for endothelial cell growth and migration. In proliferation assays, growth factor- or serum-induced DNA synthesis in three different types of human endothelial cells was abrogated by(More)
The endothelium, which forms the inner lining of blood vessels and lymphatics, participates in many physiological functions. Endothelial cell phenotypes vary in structure and function, in space and time, and in health and disease. The goal of this review is to underscore the importance of phenotypic heterogeneity as a core property of the endothelium.
Acquired abnormalities in platelets, endothelium, and their interaction occur in sepsis, immune heparin-induced thrombocytopenia (HIT), and the antiphospholipid syndrome. Although of distinct pathogeneses, these three disorders have several clinical features in common, including thrombocytopenia and the potential for life- and limb-threatening thrombotic(More)
To study the in vivo expression of the murine Tie2 gene, we have targeted the hypoxanthine phosphoribosyltransferase (Hprt) gene locus to generate two single-copy transgenic mice: T1, containing the 2,100-bp Tie2 promoter upstream from the beta-galactosidase (LacZ) gene, and T5, which also included an enhancing element originating from the first intron of(More)
ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knock-down on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely interferes with EC lumen formation. Quantitative PCR (QPCR) was(More)
In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice. Administration of LPS transiently increased the steady-state(More)