Kahena Tarhouni1,2,3, A.-L. Guihot1,2,3, Mohamed Lamine Freidja1,2,3, Bertrand Toutain1,2,3, B. Henrion1,2,3, Christophe Baufreton1,2,3, Frédéric Pinaud1,2,3, Vincent Procaccio1,2,3, Linda Grimaud1,2,3, Audrey Ayer1,2,3, Laurent Loufrani1,2,3, Françoise Lenfant1,2,3, Jean‐François Arnal1,2,3, Daniel Henrion1,2,3
1CNRS UMR 6214, Angers, France (A.L.G., L.L., D.H.)
2From the LUNAM Université and Université d’Angers, Angers, France (K.T., M.L.F., B.T., B.H., C.B., V.P., L.G., A.A., L.L., D.H.); CNRS UMR 6214, Angers, France (A.L.G., L.L., D.H.); INSERM U1083, Angers, France (L.L., D.H.); CHU (University Hospital) d’Angers, Angers, France (C.B., F.P., D.H.); and INSERM U1048, Université Toulouse III Paul Sabatier, CHU (University Hospital) de Toulouse, Toulouse, France (F.L., J.F.A.)
3INSERM U1083, Angers, France (L.L., D.H.)
Tóm tắt
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.
Methods and 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.
Conclusion—
We demonstrate the essential role of E2 and endothelial estrogen receptor α in flow-mediated remodeling of resistance arteries in vivo.
