title: Dysregulation of the angiopoietin-Tie-2 axis in sepsis and ARDS.
abstract: Dynamic changes in microvascular endothelial structure and function are pivotal in the acute inflammatory response, the body's rapid, coordinated effort to localize, sequester, and eliminate microbial invaders at their portal of entry. To achieve this, the endothelium becomes leaky and inflamed, providing innate immune cells and humoral effector molecules access to the site of infection. During sepsis this locally adaptive response becomes manifest throughout the body, leading to dangerous host consequences. Increased leakiness in the pulmonary circulation contributes to acute respiratory distress syndrome (ARDS), a complication of sepsis associated with 40% mortality. Understanding the molecular governance of vascular leak and inflammation has major diagnostic, prognostic, and potentially therapeutic implications for this common and pernicious disease. This review summarizes results from cell-based experiments, animal models, and observational human studies; together, these studies suggest that an endothelial receptor called Tie2 and its ligands, called angiopoietins, form a signaling axis key to the vascular dyshomeostasis that underlies sepsis.
authors: Harvard Medical School, Boston, MA, USA. sparikh1@bidmc.harvard.edu
authors: Samir M
authors: SM
authors: Parikh
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018805:Sepsis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042787:Receptor, TIE-2
keywords: Tie-1; Tie-2; VE-PTP; VE-cadherin; acute respiratory distress syndrome; angiopoietin-1; angiopoietin-2; infection; permeability; sepsis; vascular leakage
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