title: Emerging therapeutic strategies to prevent infection-related microvascular endothelial activation and dysfunction.
abstract: Recent evidence suggests that loss of endothelial barrier function and resulting microvascular leak play important mechanistic roles in the pathogenesis of infection-related end-organ dysfunction and failure. Several distinct therapeutic strategies, designed to prevent or limit infection-related microvascular endothelial activation and permeability, thereby mitigating end-organ injury/dysfunction, have recently been investigated in pre-clinical models. In this review, these potential therapeutic strategies, namely, VEGFR2/Src antagonists, sphingosine-1-phosphate agonists, fibrinopeptide Bβ 15-42, slit2N, secinH3, angiopoietin-1/tie-2 agonists, angiopoietin-2 antagonists, statins, atrial natriuretic peptide, and mesenchymal stromal (stem) cells, are discussed in terms of their translational potential for the management of clinical infectious diseases.
authors.affiliation: University Health Network-Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Ilyse
authors.initials: I
authors.lastname: Darwish
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
mesh_terms: D000818:Animals; D003141:Communicable Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism*
keywords: acute lung injury; emerging therapeutics; endothelium; infectious diseases; microvascular leak; sepsis