The estrogen effects on endothelial repair and mitogen-activated protein kinase activation are abolished in endothelial nitric-oxide (NO) synthase knockout mice, but not by NO synthase inhibition by N-nitro-L-arginine methyl ester
| Autor: | Cédric Filipe, Stephanie Lehoux, Chantal Dessy, Audrey Billon, Laetitia Lam Shang Leen, Pierre Gourdy, Jean-François Arnal, Vincent Benouaich, Laurent Brouchet, Alain Tedgui, Alain-Pierre Gadeau, Henrik Laurell, Jean-Luc Balligand |
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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), Centre de Recherche Cardiovasculaire de Lariboisiere, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Adaptation cardiovasculaire à l'ischemie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Pharmacothérapie, neant, UCL - MD/MINT - Département de médecine interne |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Arginine
030204 cardiovascular system & hematology MESH: Mice Knockout chemistry.chemical_compound Mice 0302 clinical medicine MESH: NG-Nitroarginine Methyl Ester Enos MESH: Animals Enzyme Inhibitors Phosphorylation MESH: Estrogen Receptor alpha Cells Cultured Mice Knockout 0303 health sciences biology Estradiol MESH: Gene Expression Regulation Enzymologic MESH: Regeneration Nitric Oxide Synthase Type III [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Nitric oxide synthase Endothelial stem cell medicine.anatomical_structure NG-Nitroarginine Methyl Ester MESH: Enzyme Inhibitors Female MESH: Endothelium Vascular MESH: Estradiol MESH: Nitric Oxide Synthase Type III MESH: Cells Cultured medicine.medical_specialty Endothelium Nitric Oxide MESH: Mitogen-Activated Protein Kinase Kinases Gene Expression Regulation Enzymologic Pathology and Forensic Medicine Nitric oxide 03 medical and health sciences MESH: Mice Inbred C57BL Internal medicine medicine Animals Regeneration MESH: Mice 030304 developmental biology Mitogen-Activated Protein Kinase Kinases MESH: Phosphorylation Estrogen Receptor alpha MESH: Tunica Intima biology.organism_classification Mice Inbred C57BL Endocrinology chemistry MESH: Nitric Oxide biology.protein Endothelium Vascular Tunica Intima Estrogen receptor alpha MESH: Female Regular Articles |
| Zdroj: | American Journal of Pathology American Journal of Pathology, American Society for Investigative Pathology, 2008, 172 (3), pp.830-8. ⟨10.2353/ajpath.2008.070439⟩ The American Journal of Pathology : cellular and molecular biology of disease, Vol. 172, no. 3, p. 830-838 (2008) |
| ISSN: | 0002-9440 1525-2191 |
| DOI: | 10.2353/ajpath.2008.070439⟩ |
| Popis: | We have previously shown that estrogen exerts a vasoprotective effect by accelerating reendothelialization after perivascular artery injury through activation of the estrogen receptor alpha. Because 17beta-estradiol (E2) is known to increase the bioavailability of nitric oxide, in this study, we used the same perivascular model to characterize the role of the endothelial nitric oxide synthase (eNOS) pathway in reendothelialization. Surprisingly, we found that the stimulatory effect of E2 on reendothelialization was not altered following pharmacological inhibition of nitric-oxide synthase enzymatic activity by N-nitro-L-arginine methyl ester, whereas it was abolished in eNOS-deficient (eNOS-/-) mice. This discrepancy between eNOS gene inactivation and the pharmacological inhibition of eNOS was confirmed in a classical model of endovascular injury. When assessing the involvement of eNOS in short-term membrane-associated signaling events induced by E2, we found that E2 stimulated phosphorylation of extracellular signal-regulated kinase 1/2 in isolated perfused carotid arteries from wild-type mice in the absence or presence of N-nitro-l-arginine methyl ester, whereas this stimulation was abolished in carotid arteries from eNOS-/- mice. Similar results were obtained in primary cultures of mouse aortic endothelial cells. These data reveal an original and unexpected role of eNOS, in which its presence but not its enzymatic activity appears to be a determinant for estrogen signaling in the endothelium. The consequences of this novel function of eNOS with respect to vascular diseases should be explored. |
| Databáze: | OpenAIRE |
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