Elevated levels of placental growth factor represent an adaptive host response in sepsis

Yano, K; Okada, Y; Beldi, G; Shih, S.C.; Bodyak, N; Okada, H; Kang, P.M.; Luscinskas, W; Robson, S.C.; Carmeliet, P; Karumanchi, S.A.; Aird, W.C. (2008). Elevated levels of placental growth factor represent an adaptive host response in sepsis. Journal of experimental medicine, 205(11), pp. 2623-31. New York, N.Y.: Rockefeller University Press 10.1084/jem.20080398

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Recently, we demonstrated that circulating levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are increased in sepsis (Yano, K., P.C. Liaw, J.M. Mullington, S.C. Shih, H. Okada, N. Bodyak, P.M. Kang, L. Toltl, B. Belikoff, J. Buras, et al. 2006. J. Exp. Med. 203:1447-1458). Moreover, enhanced VEGF/Flk-1 signaling was shown to contribute to sepsis morbidity and mortality. We tested the hypothesis that PlGF also contributes to sepsis outcome. In mouse models of endotoxemia and cecal ligation puncture, the genetic absence of PlGF or the systemic administration of neutralizing anti-PlGF antibodies resulted in higher mortality compared with wild-type or immunoglobulin G-injected controls, respectively. The increased mortality associated with genetic deficiency of PlGF was reversed by adenovirus (Ad)-mediated overexpression of PlGF. In the endotoxemia model, PlGF deficiency was associated with elevated circulating levels of VEGF, induction of VEGF expression in the liver, impaired cardiac function, and organ-specific accentuation of barrier dysfunction and inflammation. Mortality of endotoxemic PlGF-deficient mice was increased by Ad-mediated overexpression of VEGF and was blocked by expression of soluble Flt-1. Collectively, these data suggest that up-regulation of PlGF in sepsis is an adaptive host response that exerts its benefit, at least in part, by attenuating VEGF signaling.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Beldi, Guido

ISSN:

0022-1007

ISBN:

1540-9538 (Electroni

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:04

Last Modified:

04 May 2014 23:19

Publisher DOI:

10.1084/jem.20080398

Web of Science ID:

000260603200018

URI:

https://boris.unibe.ch/id/eprint/27699 (FactScience: 110174)

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