title: Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation.
abstract: BACKGROUND
  Estrogens improve endothelial function and accelerate reendothelialization after vascular injury via largely unknown mechanisms. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to positively influence endothelialization, vascular repair, and angiogenesis.
  
  
  RESULTS
  In mice subjected to sham operation, ovariectomy, or ovariectomy and estrogen replacement treatment, estrogen deficiency significantly decreased EPCs circulating in the peripheral blood and residing in the bone marrow, as well as EPCs that were in vitro expanded from spleen-derived mononuclear cells. These effects were completely prevented by estrogen replacement. Human women with increased estrogen plasma concentrations also displayed profoundly increased levels of circulating EPCs. Estrogens increase EPC numbers through a decreased apoptosis rate, which is mediated via a caspase-8-dependent pathway. Estrogen deficiency increased neointima formation after carotid artery injury in mice, but this effect was diminished by estrogen replacement therapy. In mice transplanted with green fluorescent protein-positive bone marrow, reendothelialization of injured vessel segments by bone marrow-derived cells was decreased during estrogen deficiency and increased in response to estrogen treatment.
  
  
  CONCLUSIONS
  Estrogens increase numbers of EPCs by antiapoptotic effects leading to accelerated vascular repair and decreased neointima formation.
authors.affiliation: Klinik und Poliklinik Innere Medizin III, Universität des Saarlandes, 66421 Homburg/Saar, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Strehlow
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
authors.forename: Jan
authors.initials: J
authors.lastname: Berweiler
authors.forename: Andreas
authors.initials: A
authors.lastname: Link
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Kerstin
authors.initials: K
authors.lastname: Laufs
authors.forename: Leyli
authors.initials: L
authors.lastname: Ghaeni
authors.forename: Milan
authors.initials: M
authors.lastname: Milosevic
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000172:deficiency / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000172:deficiency / Q000494:pharmacology*; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology
chemical_list: D004967:Estrogens; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D004958:Estradiol