Premium
A role for soluble HLA‐G1 in the induction of vascular cell apoptosis
Author(s) -
Cartwright Judith,
Whitley Guy,
Le Bouteiller Philippe
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1078-d
Subject(s) - apoptosis , fas ligand , microbiology and biotechnology , vascular smooth muscle , biology , western blot , trophoblast , endothelial stem cell , spiral artery , immunology , programmed cell death , fetus , placenta , endocrinology , biochemistry , pregnancy , genetics , smooth muscle , gene , in vitro
Uterine spiral artery remodelling is a crucial adaptation in early pregnancy that allows a sufficient blood supply to reach the developing fetus. We have shown that this vascular remodelling involves endothelial and vascular smooth muscle cell apoptosis triggered by the fetal‐derived trophoblast cells. Extravillous trophoblasts produce soluble HLA‐G1. We have investigated the hypothesis that soluble HLA‐G1 is an important regulator of vascular cell apoptosis. Endothelial cells (primary HUVEC or a cell line, SGHEC‐7), vascular smooth muscle cells (human aortic SMC line) or extravillous trophoblasts were incubated with recombinant sHLA‐G1 and apoptosis was monitored by time‐lapse microscopy and western blot analysis of apoptotic markers. Soluble HLA‐G1 induced apoptotic morphological changes in endothelial cells. Apoptosis was confirmed using the broad‐spectrum caspase inhibitor zVAD‐fmk, which abrogated sHLA‐G1 induced cell death. In addition, western blot analysis showed that sHLA‐G1 treated endothelial cells had increased production of the apoptotic marker cleaved PARP. Soluble HLA‐G1‐induced endothelial apoptosis was almost completely blocked in the presence of an antibody that prevents Fas/FasL interactions. Soluble HLA‐G1 also induced vascular smooth muscle cell apoptosis but had no effect on trophoblast cell survival. In conclusion, we have shown that sHLA‐G1 induces vascular cell apoptosis and that for endothelial cells this effect may be partly through the Fas/FasL system. Soluble HLA‐G1 may therefore have a role in the induction of uterine spiral artery remodelling seen in early pregnancy.