Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis. 2007

Po-Nien Tsao, and Feng-Tsan Chan, and Shu-Chen Wei, and Wu-Shiun Hsieh, and Hung-Chieh Chou, and Yi-Ning Su, and Chien-Yi Chen, and Wen-Ming Hsu, and Fon-Jou Hsieh, and Su-Ming Hsu
Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. tsaopn@ntu.edu.tw

OBJECTIVE To determine the putative role in the modulation of inflammation of a soluble form of Flt-1 (sFlt), a potent vascular endothelial growth factor antagonist, in experimental endotoxemia and sepsis. METHODS Randomized prospective experimental study. METHODS University medical laboratory. METHODS Male C56BL/6 strain mice. METHODS We investigated the expression patterns and the effects of vascular endothelial growth factor and soluble Flt-1 in experimental endotoxic shock and sepsis. The possible anti-inflammatory mechanism of soluble Flt-1 was also evaluated. RESULTS Both vascular endothelial growth factor and sFlt-1 were rapidly released from macrophages activated in vitro by lipopolysaccharide and in the plasma of endotoxemic mice. Administration of vascular endothelial growth factor enhanced proinflammatory cytokine production and mediated a dramatic increase in mortality in endotoxemic mice. Treatment with sFlt-1 attenuated inflammatory responses, inhibited recruitment of inflammatory cells into the peritoneal cavity, and improved survival in a lethal endotoxemia and cecal ligation and puncture-induced sepsis model, even when administered as late as 24 hrs after the onset of sepsis. CONCLUSIONS These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012772 Shock, Septic Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status. Endotoxin Shock,Septic Shock,Shock, Endotoxic,Shock, Toxic,Toxic Shock,Toxic Shock Syndrome,Endotoxin Shocks,Shock Syndrome, Toxic,Shock, Endotoxin,Shocks, Endotoxin,Toxic Shock Syndromes
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D016019 Survival Analysis A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. Analysis, Survival,Analyses, Survival,Survival Analyses
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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