Estradiol and progestins differentially modulate leukocyte infiltration after vascular injury

Article

关键词: RAT CAROTID-ARTERY;    ADVENTITIAL FIBROBLAST MIGRATION;    ESTROGEN-RECEPTOR-ALPHA;    NITRIC-OXIDE SYNTHASE;    BALLOON INJURY;    IN-VIVO;    PHYSIOLOGICAL CONCENTRATION;    MYOINTIMAL PROLIFERATION;    HEMATOPOIETIC-CELLS;    SKELETAL-MUSCLE;   

DOI  :  10.1161/01.CIR.0000105700.95607.49

来源: SCIE

【 摘 要 】

Background - Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17beta-estradiol, E-2) inhibits neointima formation in animal models, and the progestin medroxyprogesterone acetate (MPA) blocks this effect. This study tested the hypothesis that E-2 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 E-2, MPA, E-2 + 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. E-2 reduced the granulocyte and monocyte/macrophage populations of injured vessels by approximate to50% and increased T lymphocytes. MPA had no independent effect on inflammatory cells but completely blocked the effect of E-2. Immunohistochemical examination verified these findings and localized inflammatory cells to the adventitial and periadventitial domains of injured vessels. Conclusions - E-2 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.

【 授权许可】

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