Estradiol and progestins differentially modulate leukocyte infiltration after vascular injury.
BACKGROUND
Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17beta-estradiol, E2) inhibits neointima formation in animal models, and the progestin medroxyprogesterone acetate (MPA) blocks this effect. This study tested the hypothesis that E2 inhibits the migration of inflammatory cells, particularly granulocytes, into the rat carotid arteries after acute endoluminal injury and that MPA blocks this effect.


RESULTS
Ovariectomized rats were randomly divided into subgroups and treated with E2, MPA, E2+MPA, or vehicle and subjected to balloon injury of the right carotid artery. After 1, 3, or 7 days, rats were euthanized, and carotid arteries (injured and control) were analyzed for inflammatory cells by flow cytometry. At 1 day, granulocytes (HIS48+ and CD45+), monocyte/macrophages (Mar1+ and CD45+), and T lymphocytes (CD3+ and CD45+) were increased 26-fold, 12-fold, and 3-fold, respectively, in injured compared with contralateral control arteries of vehicle-treated rats. Granulocytes and monocyte/macrophages decreased markedly by 3 days. E2 reduced the granulocyte and monocyte/macrophage populations of injured vessels by approximately 50% and increased T lymphocytes. MPA had no independent effect on inflammatory cells but completely blocked the effect of E2. Immunohistochemical examination verified these findings and localized inflammatory cells to the adventitial and periadventitial domains of injured vessels.


CONCLUSIONS
E2 may limit the neointimal response to endoluminal vascular injury, at least in part, by limiting leukocyte entry from adventitial/periadventitial tissues into injured vessels early in the injury response.
Xing
Dongqi
D
Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294, USA. dqxing@uab.edu
Miller
Andrew
A
Novak
Lea
L
Rocha
Ricardo
R
Chen
Yiu-Fai
YF
Oparil
Suzanne
S
D000818:Animals; D016893:Carotid Stenosis / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D011372:Progestins; D004958:Estradiol; D017258:Medroxyprogesterone Acetate