Title: Elevated levels of placental growth factor represent an adaptive host response in sepsis
Authors: Yano, Kiichiro
Okada, Yoshiaki
Beldi, Guido
Shih, Shou-Ching
Bodyak, Natalya
Okada, Hitomi
Kang, Peter M
Luscinskas, William
Robson, Simon C
Carmeliet, Peter
Karumanchi, Ananth
Aird, William C # ×
Issue Date: Oct-2008
Publisher: Rockefeller univ press
Series Title: Journal of Experimental Medicine vol:205 issue:11 pages:2623-2631
Abstract: 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-PIGF 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.
ISSN: 0022-1007
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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