This Article Full Text Full Text (PDF) Supplemental Material Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Elhage, R. Articles by Bayard, F. Search for Related Content PubMed PubMed Citation Articles by Elhage, R. Articles by Bayard, F.

(American Journal of Pathology. 2005;167:267-274.)
© 2005 American Society for Investigative Pathology

The Atheroprotective Effect of 17ß-Estradiol Depends on Complex Interactions in Adaptive Immunity

Rima Elhage^*, Pierre Gourdy^*, Jacek Jawien, Laurent Brouchet^*, Caroine Castano^*, Catherine Fievet, Göran K. Hansson, Jean-François Arnal^* and Francis Bayard^*

From INSERM U589,^* IFR31, Institut L. Bugnard, Toulouse, France; INSERM U545 Institut Pasteur, Lille, France; and the Center for Molecular Medicine and Department of Medicine, Karolinska Institute, Stockholm, Sweden

Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak development of immunodeficient ApoE^–/–/recombination activating gene 2 (RAG-2^–/–) double-deficient mice was insensitive to estradiol. In the present work, we demonstrate that the reconstitution of ApoE^–/–/RAG-2^–/– with bone marrow from immunocompetent ApoE^–/–/RAG-2^+/+ mice restores the protective effect of estradiol on fatty streak constitution. We extended this demonstration to the model of low-density lipoprotein receptor-deficient mice, establishing the obligatory role of mature lymphocytes in this process. We then investigated whether the protective effect of estradiol was mediated by a specific lymphocyte subpopulation by studying the hormonal effect on fatty streak constitution in recently developed models of ApoE^–/– mice deficient in selective T-lymphocyte subsets (either TCRß⁺, CD4⁺, CD8⁺, or TCR⁺ lymphocytes) or B lymphocytes. In all these specifically immunodeficient mice, estradiol administration to ovariectomized mice conferred protection as in immunocompetent ApoE^–/– mice, clearly demonstrating that no single lymphocyte subpopulation was specifically required for this effect. These results point to additional lymphocyte-dependent mechanisms such as modulating the interactions among lymphocytes and between lymphocytes and endothelial and/or antigen-presenting cells.

This article has been cited by other articles:

				A. Billon-Gales, C. Fontaine, V. Douin-Echinard, L. Delpy, H. Berges, B. Calippe, F. Lenfant, H. Laurell, J.-C. Guery, P. Gourdy, et al. Endothelial Estrogen Receptor-{alpha} Plays a Crucial Role in the Atheroprotective Action of 17{beta}-Estradiol in Low-Density Lipoprotein Receptor-Deficient Mice Circulation, December 22, 2009; 120(25): 2567 - 2576. [Abstract] [Full Text] [PDF]

				A. Billon-Gales, C. Fontaine, C. Filipe, V. Douin-Echinard, M.-J. Fouque, G. Flouriot, P. Gourdy, F. Lenfant, H. Laurell, A. Krust, et al. The transactivating function 1 of estrogen receptor {alpha} is dispensable for the vasculoprotective actions of 17{beta}-estradiol PNAS, February 10, 2009; 106(6): 2053 - 2058. [Abstract] [Full Text] [PDF]

				P. Gourdy, A. Schambourg, C. Filipe, V. Douin-Echinard, B. Garmy-Susini, B. Calippe, F. Terce, F. Bayard, and J.-F. Arnal Transforming Growth Factor Activity Is a Key Determinant for the Effect of Estradiol on Fatty Streak Deposit in Hypercholesterolemic Mice Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2214 - 2221. [Abstract] [Full Text] [PDF]