Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation.
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.
Strehlow
Kerstin
K
Klinik und Poliklinik Innere Medizin III, Universität des Saarlandes, 66421 Homburg/Saar, Germany.
Werner
Nikos
N
Berweiler
Jan
J
Link
Andreas
A
Dirnagl
Ulrich
U
Priller
Josef
J
Laufs
Kerstin
K
Ghaeni
Leyli
L
Milosevic
Milan
M
Böhm
Michael
M
Nickenig
Georg
G
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
D004967:Estrogens; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D004958:Estradiol