Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium.
Although the accelerative effect of 17beta-estradiol (E2) on endothelial regrowth has been clearly demonstrated, the local cellular events accounting for this beneficial vascular action are still uncertain. In the present work, we compared the kinetics of endothelial healing of mouse carotid arteries after endovascular and perivascular injury. Both basal reendothelialization as well as the accelerative effect of E2 were similar in the two models. Three days after endothelial denudation, a regenerative area was observed in both models, characterized by similar changes in gene expression after injury, visualized by en face confocal microscopy (EFCM). A precise definition of the injury limits was only possible with the perivascular model, since it causes a complete and lasting decellularization of the media. Using this model, we demonstrated that the migration of uninjured endothelial cells precedes proliferation (bromodeoxyuridine incorporation) and that these events occur at earlier time points with E2 treatment. We have also identified an uninjured retrograde zone as an intimate component of the endothelial regeneration process. Thus, in the perivascular model, the regenerative area can be subdivided into a retrograde zone and a reendothelialized area. Importantly, both areas are significantly enlarged by E2. In conclusion, the combination of the electric perivascular injury model and EFCM is well adapted to the visualization of the endothelial monolayer and to investigate cellular events involved in reendothelialization. This process is accelerated by E2 as a consequence of the retrograde commitment of an uninjured endothelial zone to migrate and proliferate, contributing to an enlargement of the regenerative area.
Filipe
Cédric
C
Institut National de la Santé et de la Recherche Médicale (INSERM) U858, I2MR, Equipe 9, Université de Toulouse III Paul Sabatier and Centre Hospitalier Universitaire de Toulouse-Rangueil, Toulouse, France.
Lam Shang Leen
Laetitia
L
Brouchet
Laurent
L
Billon
Audrey
A
Benouaich
Vincent
V
Fontaine
Vincent
V
Gourdy
Pierre
P
Lenfant
Françoise
F
Arnal
Jean-François
JF
Gadeau
Alain-Pierre
AP
Laurell
Henrik
H
D000818:Animals; D016026:Bone Marrow Transplantation; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004343:Drug Implants; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D010052:Ovariectomy; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014945:Wound Healing
D004343:Drug Implants; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004958:Estradiol