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Vascular smooth muscle cell apoptosis is a critical event in vessel remodeling during human pregnancy
Author(s) -
Keogh Rosemary Jeanne,
Whitley Guy,
Harris Lynda,
Baker Philip,
Aplin John,
Cartwright Judith
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
Subject(s) - spiral artery , trophoblast , apoptosis , biology , microbiology and biotechnology , receptor , decidua , vascular smooth muscle , endocrinology , medicine , fetus , pregnancy , placenta , smooth muscle , genetics , biochemistry
Remodeling of resistance arteries typically involves medial thickening through smooth muscle cells (SMC) hyperplasia and extra‐cellular matrix deposition. The result is reduced lumen diameter and increased resistance. When uterine spiral arteries remodel in human pregnancy the opposite occurs. Loss of endothelium and SMC results in medial ablation, luminal expansion and decreased resistance. This change facilitates greater blood flow to the fetus however the underlying mechanisms are poorly defined. Shallow or incomplete fetal trophoblast invasion and limited remodeling are associated with pregnancy complications like pre‐eclampsia. We tested the hypothesis that vascular SMC apoptosis is a key step in spiral artery remodeling during pregnancy and focused on interactions between trophoblast and SMC. Co‐culture of human aortic SMC (HASMC) with primary first trimester human cytotrophoblasts (CTB) or a trophoblast cell line, SGHPL‐4, caused HASMC apoptosis and could be blocked by caspase inhibition with zVAD‐fmk. CTB in culture produced the apoptotic cytokines Fas ligand and TRAIL and receptors for these cytokines were detected in term spiral artery sections. A Fas‐activating antibody or rhTRAIL induced HASMC apoptosis; blocking Fas or TRAIL receptor activation significantly inhibited CTB‐induced HASMC apoptosis in co‐culture. We propose that trophoblast‐derived apoptotic cytokines cause SMC apoptosis in uterine spiral arteries thus contributing to vessel remodeling during pregnancy. Supported by a Wellcome Trust UK grant (069939).