title: Key role of estrogens and endothelial estrogen receptor α in blood flow-mediated remodeling of resistance arteries.
abstract: OBJECTIVE
  Flow- (shear stress-)mediated outward remodeling of resistance arteries is involved in collateral growth during postischemic revascularization. As this remodeling is especially important during pregnancy, we hypothesized that estrogens may be involved. A surgical model eliciting a local increase in blood flow in 1 mesenteric resistance artery was used in 3-month-old ovariectomized female rats either treated with 17-β-estradiol (E2) or left untreated.
  
  
  RESULTS
  After 14 days, arterial diameter was greater in high-flow arteries than in normal-flow vessels. An ovariectomy suppressed high-flow remodeling, while E2 restored it. High-flow remodeling was absent in mice lacking the estrogen receptor α but not estrogen receptor β. The kinetics of inflammatory marker expression, macrophage infiltration, oxidative stress, and metaloproteinases expression were not altered by the absence of E2 after 2 and 4 days, that is, during remodeling. Nevertheless, E2 was required for the increase in endothelial nitric oxide synthase expression and activation at day 4 when diameter expansion occurs. Finally, the impact of E2 on the endothelium appeared crucial for high-flow remodeling, as this E2 action was abrogated in mice lacking endothelial NOS, as well as in Tie2-Cre(+) ERα(f/f) mice.
  
  
  CONCLUSIONS
  We demonstrate the essential role of E2 and endothelial estrogen receptor α in flow-mediated remodeling of resistance arteries in vivo.
authors.affiliation: LUNAM Université and Université d’Angers, Angers, France.
authors.forename: K
authors.initials: K
authors.lastname: Tarhouni
authors.forename: A L
authors.initials: AL
authors.lastname: Guihot
authors.forename: M L
authors.initials: ML
authors.lastname: Freidja
authors.forename: B
authors.initials: B
authors.lastname: Toutain
authors.forename: B
authors.initials: B
authors.lastname: Henrion
authors.forename: C
authors.initials: C
authors.lastname: Baufreton
authors.forename: F
authors.initials: F
authors.lastname: Pinaud
authors.forename: V
authors.initials: V
authors.lastname: Procaccio
authors.forename: L
authors.initials: L
authors.lastname: Grimaud
authors.forename: A
authors.initials: A
authors.lastname: Ayer
authors.forename: L
authors.initials: L
authors.lastname: Loufrani
authors.forename: F
authors.initials: F
authors.lastname: Lenfant
authors.forename: J F
authors.initials: JF
authors.lastname: Arnal
authors.forename: D
authors.initials: D
authors.lastname: Henrion
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D051242:Caveolin 1 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage*; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000172:deficiency / Q000235:genetics; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics; D015914:Estrogen Replacement Therapy; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D010052:Ovariectomy; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: C495541:Cav1 protein, mouse; C495537:Cav1 protein, rat; D051242:Caveolin 1; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009569:Nitric Oxide; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse