title: Platelet-rich plasma extract prevents pulmonary edema through angiopoietin-Tie2 signaling.
abstract: Increased vascular permeability contributes to life-threatening pathological conditions, such as acute respiratory distress syndrome. Current treatments for sepsis-induced pulmonary edema rely on low-tidal volume mechanical ventilation, fluid management, and pharmacological use of a single angiogenic or chemical factor with antipermeability activity. However, it is becoming clear that a combination of multiple angiogenic/chemical factors rather than a single factor is required for maintaining stable and functional blood vessels. We have demonstrated that mouse platelet-rich plasma (PRP) extract contains abundant angiopoietin (Ang) 1 and multiple other factors (e.g., platelet-derived growth factor), which potentially stabilize vascular integrity. Here, we show that PRP extract increases tyrosine phosphorylation levels of Tunica internal endothelial cell kinase (Tie2) and attenuates disruption of cell-cell junctional integrity induced by inflammatory cytokine in cultured human microvascular endothelial cells. Systemic injection of PRP extract also increases Tie2 phosphorylation in mouse lung and prevents endotoxin-induced pulmonary edema and the consequent decreases in lung compliance and exercise intolerance resulting from endotoxin challenge. Soluble Tie2 receptor, which inhibits Ang-Tie2 signaling, suppresses the ability of PRP extract to inhibit pulmonary edema in mouse lung. These results suggest that PRP extract prevents endotoxin-induced pulmonary edema mainly through Ang-Tie2 signaling, and PRP extract could be a potential therapeutic strategy for sepsis-induced pulmonary edema and various lung diseases caused by abnormal vascular permeability.
authors: Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Tadanori
authors: T
authors: Mammoto
authors: Amanda
authors: A
authors: Jiang
authors: Elisabeth
authors: E
authors: Jiang
authors: Akiko
authors: A
authors: Mammoto
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D016913:Blood Component Transfusion; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010949:Plasma; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D042787:Receptor, TIE-2 / Q000378:metabolism*; D018805:Sepsis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D004731:Endotoxins; D042787:Receptor, TIE-2; C079086:Tek protein, mouse
keywords: Tunica internal endothelial cell kinase; angiopoietin; lung; platelet-rich plasma extract; vascular permeability