title: Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats.
abstract: BACKGROUND
  Estrogen replacement attenuates the increased risk of cardiovascular disease in postmenopausal women. Recent studies using an in vitro culture system have shown that estrogen inhibits endothelial cell (EC) apoptosis. The in vivo relevance of this finding, however, is not defined. To do so, we have developed a rat vascular injury model in which EC apoptosis induced by hydrogen peroxide plays a role.
  
  
  RESULTS
  Intracarotid arterial administration of 0.01 mmol/L hydrogen peroxide for 5 minutes evoked EC apoptosis after 6 to 24 hours, determined by nuclear staining with Hoechst 33342, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and electron microscopy. Apoptosis was associated with EC loss and was followed by EC regeneration at 72 hours and neointima formation at 1 to 2 weeks. Estradiol replacement in ovariectomized female Wistar rats decreased the rate of apoptotic ECs by approximately 50%, assayed by nuclear morphology of en face specimens, resulting in increased remaining ECs and decreased neointima formation. Progesterone did not influence the effects of estradiol on EC apoptosis.
  
  
  CONCLUSIONS
  These results provide new insight into the cardioprotective action of estrogen as well as a paradigm of the response-to-injury hypothesis.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sudoh
authors.forename: K
authors.initials: K
authors.lastname: Toba
authors.forename: M
authors.initials: M
authors.lastname: Akishita
authors.forename: J
authors.initials: J
authors.lastname: Ako
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Liang
authors.forename: Y
authors.initials: Y
authors.lastname: Ohike
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: I
authors.initials: I
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: M
authors.initials: M
authors.lastname: Eto
authors.forename: Y
authors.initials: Y
authors.lastname: Ouchi
mesh_terms: D000818:Animals; D017209:Apoptosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004967:Estrogens; D006861:Hydrogen Peroxide