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Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2008 Jun; Vol. 294 (6), pp. H2822-30. Date of Electronic Publication: 2008 Apr 25. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Animals
Bone Marrow Transplantation
Carotid Artery Injuries pathology
Carotid Artery Injuries physiopathology
Cell Movement
Cell Proliferation
Disease Models, Animal
Drug Implants
Endothelium, Vascular pathology
Endothelium, Vascular physiopathology
Estradiol administration & dosage
Female
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Immunohistochemistry
Kinetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal methods
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular physiopathology
Ovariectomy
Recombinant Fusion Proteins metabolism
Carotid Artery Injuries metabolism
Endothelium, Vascular metabolism
Estradiol metabolism
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 294
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18441207
- Full Text :
- https://doi.org/10.1152/ajpheart.00129.2008