HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2822    most recent 00129.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Filipe, C. Articles by Laurell, H. PubMed PubMed Citation Articles by Filipe, C. Articles by Laurell, H.

Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium

¹Institut National de la Santé et de la Recherche Médicale (INSERM) U858, I2MR, Équipe 9, Université de Toulouse III Paul Sabatier and Centre Hospitalier Universitaire de Toulouse-Rangueil, Toulouse; and ²Institut National de la Santé et de la Recherche Médicale (INSERM) U828, Université de Bordeaux 2, Pessac, France

Submitted 6 February 2008 ; accepted in final form 16 April 2008

Although the accelerative effect of 17β-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.

endothelial regeneration; arterial injury; estrogen; carotid injury model; en face confocal microscopy