title: The angiopoietin-Tie2 signaling axis in the vascular leakage of systemic inflammation.
abstract: The ability of small blood vessels to undergo rapid, reversible morphological changes is essential for the adaptive response to tissue injury or local infection. A canonical feature of this response is transient hyperpermeability. However, when leakiness is profound or persistent, adverse consequences accrue to the host, including organ dysfunction and shock. A growing body of literature identifies the Tie2 receptor, a transmembrane tyrosine kinase highly enriched in the endothelium, as an important regulator of vascular barrier function in health and in disease. The principal ligands of Tie2, Angiopoietins 1 and 2, exert opposite effects on this receptor in the context of inflammation. This review will focus on recent studies that have illuminated novel aspects of the exquisitely controlled Tie2 signaling axis while proposing unanswered questions and future directions for this field of study.
authors.affiliation: Center for Vascular Biology Research; Beth Israel Deaconess Medical Center and Harvard Medical School ; Boston, MA USA.
authors.forename: Katelyn E
authors.initials: KE
authors.lastname: Milam
authors.affiliation: Center for Vascular Biology Research; Beth Israel Deaconess Medical Center and Harvard Medical School ; Boston, MA USA ; Division of Nephrology; Beth Israel Deaconess Medical Center and Harvard Medical School ; Boston, MA USA.
authors.forename: Samir M
authors.initials: SM
authors.lastname: Parikh
keywords: ARDS; Angiopoietin; Angpt, angiopoietin; EC, endothelial cell; MAPK, mitogen-activated protein kinase; PI3K, phosphatidylinositol-3-kinase; Tie1; Tie2; VE-PTP; VE-PTP, vascular endothelial protein tyrosine phosphatase; VE-cadherin, vascular endothelial cadherin; VEGF, vascular endothelial growth factor; anthrax; barrier function; endothelium; inflammation; lung injury; malaria; respiratory distress; sepsis; siRNA, small interfering RNA; vascular leakage
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