Transforming Growth Factor Activity Is a Key Determinant for the Effect of Estradiol on Fatty Streak Deposit in Hypercholesterolemic Mice
| Autor: | Barbara Garmy-Susini, Cédric Filipe, Bertrand Calippe, Alexia Schambourg, François Tercé, Pierre Gourdy, Victorine Douin-Echinard, Jean-François Arnal, Francis Bayard |
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| Přispěvatelé: | Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de diabétologie, Pôle Cardio-Vasculaire et Métabolique, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Departement /u563 : Lipoproteines et Mediateurs Lipidiques, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) |
| Rok vydání: | 2007 |
| Předmět: |
MESH: Interleukin-12
MESH: Signal Transduction MESH: Interleukin-10 medicine.medical_treatment MESH: Mice Knockout MESH: Drug Implants MESH: Antibodies Monoclonal MESH: Atherosclerosis Mice MESH: Transforming Growth Factor beta1 0302 clinical medicine MESH: Animals MESH: Bone Marrow Transplantation Aorta Bone Marrow Transplantation Drug Implants Mice Knockout 0303 health sciences Estradiol Antibodies Monoclonal MESH: Hypercholesterolemia Interleukin MESH: Aorta MESH: Apolipoproteins E Interleukin-12 Interleukin-10 Cytokine 030220 oncology & carcinogenesis Disease Progression Female MESH: Disease Progression MESH: Estradiol medicine.symptom Cardiology and Cardiovascular Medicine MESH: Whole-Body Irradiation Whole-Body Irradiation Signal Transduction medicine.medical_specialty MESH: Interferon-gamma medicine.drug_class Ratón Ovariectomy Hypercholesterolemia MESH: Ovariectomy Inflammation Biology Proinflammatory cytokine Transforming Growth Factor beta1 Interferon-gamma 03 medical and health sciences Apolipoproteins E MESH: Mice Inbred C57BL Internal medicine medicine Animals MESH: Smad3 Protein Smad3 Protein MESH: Mice 030304 developmental biology Fatty streak Atherosclerosis Mice Inbred C57BL Disease Models Animal Endocrinology Receptors LDL MESH: Receptors LDL Estrogen MESH: Disease Models Animal MESH: Female Transforming growth factor |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2007, 27 (10), pp.2214-21. ⟨10.1161/ATVBAHA.107.150300⟩ Arteriosclerosis, Thrombosis, and Vascular Biology, 2007, 27 (10), pp.2214-21. ⟨10.1161/ATVBAHA.107.150300⟩ |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.107.150300 |
| Popis: | Objective— Whereas estradiol prevents fatty streak deposit in immunocompetent apoE −/− or LDLr −/− mice, it is totally ineffective in immunodeficient mice, underlining the key role of immunoinflammation in this effect. In the present work, the role of several major pro- and antiinflammatory cytokines involved in the atheromatous process was evaluated in the effect of estradiol on fatty streak constitution. Methods and Results— The preventive effect of estradiol was fully maintained in LDLr −/− mice grafted with bone marrow from either IFN-γ or interleukin (IL)-12–deficient mice, showing that this beneficial effect was not mediated through a specific decrease in the production of these 2 proinflammatory cytokines. Furthermore, IL-10 −/− apoE −/− mice remained protected by estradiol, excluding a significant contribution of this antiinflammatory cytokine. In contrast, the protective effect of estradiol was (1) associated with enhanced aortic expression of TGF-β1 in apoE −/− mice during early steps of atherogenesis; (2) abolished and even reversed in apoE −/− mice administered with a neutralizing anti–TGF-β antibody; (3) abolished in LDLr −/− mice grafted with bone marrow from Smad3-deficient mice. Conclusions— The status of the TGF-β pathway crucially determines the antiatherogenic effect of estradiol in hypercholesterolemic mice, whereas neither IFN-γ, IL-12, nor IL-10 are specifically involved in this protection. |
| Databáze: | OpenAIRE |
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