the synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis合成tie2兴奋剂肽vasculotide防止血管渗漏和降低小鼠腹腔脓毒症的死亡率.pdfVIP

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the synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis合成tie2兴奋剂肽vasculotide防止血管渗漏和降低小鼠腹腔脓毒症的死亡率.pdf

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the synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis合成tie2兴奋剂肽vasculotide防止血管渗漏和降低小鼠腹腔脓毒症的死亡率

Kümpers et al. Critical Care 2011, 15:R261 /content/15/5/R261 RESEARCH Open Access The synthetic Tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis 1* 2 2,3 4 4 2 Philipp Kümpers , Faikah Gueler , Sascha David , Paul Van Slyke , Daniel J Dumont , Joon-Keun Park , 5 3 1 2 2 Clemens L Bockmeyer , Samir M Parikh , Hermann Pavenstädt , Hermann Haller and Nelli Shushakova Abstract Introduction: Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non- redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis. Methods: Polymicrobial abdominal sepsis in C57BL6 mice was induced by cecal-ligation-and-puncture (CLP). Mice were treated with different dosages of VT or equal volume of phosphate-buffered saline (PBS). Sham-operated animals served as time-matched controls. Results: Systemic administration of VT induced long-lasting Tie2 activation in vivo. VT protected against sepsis- induced endothelial barrier dysfunction, as evidenced by attenuation of vascular leakage and leukocyte transmigration into the peritoneal cavity. Histological analysis revealed that VT treatment ameliorated leukocyte infiltration in kidneys of septic mice, probably