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.

Keywords: :

• endothelium
• microvascular leak
• emerging therapeutics
• infectious diseases
• sepsis
• acute lung injury

Submitted

04/01/13

Revised

07/11/13

Accepted

07/12/13

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

Grant support provided to support this work by a Canada Research Chair in Infectious Diseases and Inflammation from the Canadian Institutes of Health Research (WCL).