Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans

DSpace/Manakin Repository

Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans

Citable link to this page

. . . . . .

Title: Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans
Author: Schultz, Aylit; Parikh, Samir Mukund; Mammoto, Tadanori; Yuan, Hai-Tao; Christiani, David C.; Karumanchi, Subbian Ananth; Sukhatme, Vikas Pandurang

Note: Order does not necessarily reflect citation order of authors.

Citation: Parikh, Samir M., Tadanori Mammoto, Aylit Schultz, Hai-Tao Yuan, David Christiani, S. Ananth Karumanchi, and Vikas P. Sukhatme. 2006. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Medicine 3(3): e46.
Full Text & Related Files:
Abstract: Background: Acute respiratory distress syndrome (ARDS) is a devastating complication of numerous underlying conditions, most notably sepsis. Although pathologic vascular leak has been implicated in the pathogenesis of ARDS and sepsis-associated lung injury, the mechanisms promoting leak are incompletely understood. Angiopoietin-2 (Ang-2), a known antagonist of the endothelial Tie-2 receptor, was originally described as a naturally occurring disruptor of normal embryonic vascular development otherwise mediated by the Tie-2 agonist angiopoietin-1 (Ang-1). We hypothesized that Ang-2 contributes to endothelial barrier disruption in sepsis-associated lung injury, a condition involving the mature vasculature. Methods and Findings: We describe complementary human, murine, and in vitro investigations that implicate Ang-2 as a mediator of this process. We show that circulating Ang-2 is significantly elevated in humans with sepsis who have impaired oxygenation. We then show that serum from these patients disrupts endothelial architecture. This effect of sepsis serum from humans correlates with measured Ang-2, abates with clinical improvement, and is reversed by Ang-1. Next, we found that endothelial barrier disruption can be provoked by Ang-2 alone. This signal is transduced through myosin light chain phosphorylation. Last, we show that excess systemic Ang-2 provokes pulmonary leak and congestion in otherwise healthy adult mice. Conclusions: Our results identify a critical role for Ang-2 in disrupting normal pulmonary endothelial function.
Published Version: doi:10.1371/journal.pmed.0030046
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334221/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4879207

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters