Published online before print December 29, 2003, doi: 10.1161/01.CIR.0000105700.95607.49
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(Circulation. 2004;109:234-241.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Estradiol and Progestins Differentially Modulate Leukocyte Infiltration After Vascular Injury
From the Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine (D.X., A.M., Y.-F.C., S.O.), and the Division of Transplantation Surgery, Department of Surgery, University of Alabama at Birmingham (L.N.); and Novartis Pharmaceuticals, East Hanover, NJ (R.R.).
Correspondence to Dongqi Xing, MD, PhD, 1014 Zeigler Research Building, University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294. E-mail dqxing{at}uab.edu
Received April 24, 2003; de novo received July 16, 2003; revision received September 11, 2003; accepted September 12, 2003.
Background— Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17ß-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.
Methods and 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 
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.
Key Words: restenosis • inflammation • leukocytes • vessels • women
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