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

Kiichiro Yano., et al.  2008. J. Exp. Med. 205 (11): 2623-31

Speaker: Juin-Wei Chen (陳君瑋)                              Time: 15:00~16:00, Mar. 11, 2009

Commentator: Dr. Huan-Yao Lei (黎煥耀 老師)       Place: Room 601

Abstract:

      Placental growth factor (PlGF) is a member of vascular endothelial growth factors (VEGFs) which are generally thought to be related with angiogenesis, migration, and survival of endothelial cells. In some particular conditions such as sepsis, the expression levels of VEGF and PlGF were found to be increased. The authors wondered whether the increase of PlGF is as associated with sepsis lethality as VEGF. In animal models with LPS administration and cecal ligation puncture (CLP), PlGF-deficient mice had higher mortality, VEGF, and proiflammatory cytokine, IL-6. Moreover,challenge of LPS or CLP in PlGF-deficient mice led to apparent cardiac dysfuction and vascular leakage occurred in several organs especially in the liver. PlGF-deficiency, however, exacerbates the sepsis in the mice. Additionally, in LPS challenged PlGF-KO mice, the expression of some inflammatory and coagulation mediators such as cell adhesion molecules (CAMs), selectins, COX-2 and PAI-1 were changed in several organs especially in the liver, where the authors noted liver damage and leukocyte infiltration. Since the mortality increased in the LPS challenged PlGF-deficient mice with the increased VEGF, which is previously considered as an important determinant of sepsis mortality, the authors rescued the mortality by overexpression of PlGF. Subsequently, they proved that overexpression of VEGF would exacerbate the mortality, and the overexpression of s-Flt-1 (soluble receptor of VEGF) could rescue the mortality in LPS-challenged PlGF-KO mice.

References:

1.      Yano, K., et al.  2006. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. JEM. 203, 1447-58

2.      Nagy, J. A., et al. 2003. VEGF-A(164/165) and PlGF: roles in angiogenesis and arteriogenesis. Trends Cardiovasc Med. 13, 169-75