1. Hydroxychloroquine partially prevents endothelial dysfunction induced by anti-beta-2-GPI antibodies in an in vivo mouse model of antiphospholipid syndrome
- Author
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Urbanski, Geoffrey, Caillon, Antoine, Poli, Caroline, Kauffenstein, Gilles, Begorre, Marc-Antoine, Loufrani, Laurent, Henrion, Daniel, Belizna, Cristina, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
- Subjects
Physiology ,lcsh:Medicine ,Cardiovascular Medicine ,Biochemistry ,Vascular Medicine ,Mice ,Immune Physiology ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Immune System Proteins ,Neurochemistry ,Animal Models ,Neurotransmitters ,Arteries ,Hematology ,Antiphospholipid Syndrome ,Antibodies, Anti-Idiotypic ,Mesenteric Arteries ,Vasodilation ,Experimental Organism Systems ,beta 2-Glycoprotein I ,Cardiovascular Diseases ,Anatomy ,Neurochemicals ,Hydroxychloroquine ,Research Article ,Immunology ,Mouse Models ,Research and Analysis Methods ,Nitric Oxide ,Antibodies ,Model Organisms ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Animals ,Humans ,Endothelium ,Immunoassays ,Blood Coagulation ,Coagulation Disorders ,lcsh:R ,Biology and Life Sciences ,Proteins ,Thrombosis ,Acetylcholine ,Disease Models, Animal ,Oxidative Stress ,Animal Studies ,Immunologic Techniques ,Cardiovascular Anatomy ,Blood Vessels ,lcsh:Q ,Neuroscience - Abstract
Background Antiphospholipid syndrome is associated with endothelial dysfunction, which leads to thrombosis and early atheroma. Given that hydroxychloroquine has anti-thrombotic properties in lupus, we hypothesized that it could reduce endothelial dysfunction in an animal model of antiphospholipid syndrome. We evaluated the effect of hydroxychloroquine in preventing endothelial dysfunction in a mouse model of antiphospholipid syndrome. Methods Antiphospholipid syndrome was induced by an injection of monoclonal anti-beta-2-GPI antibodies. Vascular reactivity was evaluated in mesenteric resistance arteries isolated from mice 3 weeks (APL3W) after receiving a single injection of anti-beta-2-GPI antibodies and after 3 weeks of daily oral hydroxychloroquine treatment (HCQ3W) compared to control mice (CT3W). We evaluated endothelial dysfunction by measuring acetylcholine-mediated vasodilation. A pharmacological approach was used to evaluate NO synthase uncoupling (tetrahydrobiopterin) and the generation of reactive oxygen species (Tempol). Results Impaired acetylcholine-mediated dilation was evidenced in mice 3 weeks after anti-beta-2-GPI antibodies injection compared to CT3W, by reduced maximal dilation (p
- Published
- 2018