Endothelial estrogen receptor {alpha} plays an essential role in the coronary and myocardial protective effects of estradiol in ischemia/reperfusion
| Autor: | Françoise Lenfant, Ji Gao, Isabelle Remy-Jouet, Isabelle Fourquaux, Jean-Paul Henry, Christian Thuillez, Julie Favre, Audrey Billon-Galés, Vincent Richard, Jean-François Arnal |
|---|---|
| Přispěvatelé: | Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), 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), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Simon, Marie Francoise, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Time Factors
Vasodilator Agents Estrogen receptor Blood Pressure Vasodilation 030204 cardiovascular system & hematology MESH: Mice Knockout MESH: Drug Implants MESH: Dose-Response Relationship Drug Mice 0302 clinical medicine Heart Rate MESH: Coronary Vessels MESH: Animals MESH: Endothelial Cells Endothelial dysfunction MESH: Heart Rate MESH: Bone Marrow Transplantation MESH: Estrogen Receptor alpha Bone Marrow Transplantation Drug Implants Mice Knockout 0303 health sciences Estradiol Estrogen Replacement Therapy MESH: Reactive Oxygen Species MESH: Blood Pressure Coronary Vessels MESH: Myocardial Reperfusion Injury medicine.anatomical_structure MESH: Uterus Female MESH: Estradiol Cardiology and Cardiovascular Medicine MESH: Transplantation Chimera medicine.medical_specialty MESH: Myocardium Endothelium medicine.drug_class Ovariectomy Ischemia MESH: Ovariectomy Myocardial Reperfusion Injury MESH: Vasodilation 03 medical and health sciences In vivo MESH: Mice Inbred C57BL Internal medicine medicine Animals MESH: Mice 030304 developmental biology Transplantation Chimera Dose-Response Relationship Drug business.industry Myocardium Uterus MESH: Time Factors Estrogen Receptor alpha Endothelial Cells medicine.disease MESH: Estrogen Replacement Therapy MESH: Vasodilator Agents Mice Inbred C57BL Disease Models Animal Endocrinology Estrogen MESH: Disease Models Animal Reactive Oxygen Species business MESH: Female Ex vivo |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, 30 (12), pp.2562-7. ⟨10.1161/ATVBAHA.110.213637⟩ Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2010, 30 (12), pp.2562-7. ⟨10.1161/ATVBAHA.110.213637⟩ |
| ISSN: | 1079-5642 1524-4636 |
| DOI: | 10.1161/ATVBAHA.110.213637⟩ |
| Popis: | Objective— To assess the coronary endothelial protective effects of 17β-estradiol (E2) and the role of estrogen receptor (ER) α in ischemia/reperfusion (I/R). Methods and Results— E2 exerts protective effects in cardiac I/R. However, the implication in vivo of the endothelium and the cellular targets of the anti-ischemic effects of E2 are unknown. Mice were subjected to I/R (30 minutes of I and 1 hour of R) in vivo, after which acetylcholine-induced relaxation of isolated coronary segments was assessed ex vivo. I/R induced a coronary endothelial dysfunction in untreated ovariectomized mice that was prevented by long-term treatment with E2 in wild-type, but not in ERα −/− , mice. Chimeric mice inactivated for ERα in the hematopoietic compartment remained protected by E2. Further inactivation of endothelial ERα abolished the protective action of E2 on coronary endothelial function in Tie2-Cre(+) ERα f/f mice. More importantly, E2 significantly limited infarct size in wild-type mice but not in mice deficient in endothelial ERα, even in the presence of hematopoietic ERα. Conclusion— Endothelial ERα plays a crucial role in the E2-induced prevention of endothelial dysfunction after I/R. To our knowledge, we demonstrate for the first time, by using unique genetically modified mice, that targeting endothelial protection per se can confer cardiomyocyte protection in I/R. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|