title: The role of vascular smooth muscle cell apoptosis and migration during uterine spiral artery remodeling in normal human pregnancy.
abstract: During human uterine spiral artery (SpA) remodeling, vascular smooth muscle cells (VSMCs) are lost and replaced by fibrinoid, incorporating extravillous trophoblast (EVT) cells. The aim of the current study was to determine the relative contributions of apoptosis and migration to VSMC loss during SpA remodeling. Immunohistochemistry (Apoptag, active caspase 3, lamin) of placental bed biopsies (8-20 wk gestation) demonstrated apoptotic cells in all samples; double immunolabeling identified these as trophoblasts, leukocytes, and endothelial cells. In total, 294 SpAs were studied, and only one apoptotic VSMC was identified. H-caldesmon-immunopositive VSMCs were observed surrounding and separate from SpA walls in partially remodeled vessels; the highest level of VSMC migration was observed in vessels with associated EVT cells (number of migrated cells 6.4 ± 1.2; distance migrated 3.5 ± 0.3 pixels) compared with those without (number of migrated cells 3.6 ± 0.5, P<0.001; distance migrated 2.8 ± 0.1 pixels, P<0.0001). VEGF-A, VEGF-C, TGF-β1, and Ang-2 all stimulated human aorta VSMC invasion in vitro, although EVT cell culture supernatants did not. In summary, apoptosis is unlikely to play a major role in loss of VSMCs from SpAs during remodeling in normal pregnancy, but VSMCs appear to migrate away from the wall of the SpA, an effect enhanced by the presence of EVT cells.
authors.affiliation: Reproductive and Vascular Biology Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
authors.forename: Judith N
authors.initials: JN
authors.lastname: Bulmer
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Innes
authors.forename: Joanne
authors.initials: J
authors.lastname: Levey
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Robson
authors.forename: Gendie E
authors.initials: GE
authors.lastname: Lash
mesh_terms: D042702:Angiopoietin-2 / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D034882:Lamins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D055988:Uterine Artery / Q000166:cytology* / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology
chemical_list: D042702:Angiopoietin-2; D002148:Calmodulin-Binding Proteins; D034882:Lamins; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D014568:Urokinase-Type Plasminogen Activator; C505407:CASP3 protein, human; D053148:Caspase 3; D020782:Matrix Metalloproteinases