Pharmacological inhibition of the F 1 -ATPase/P2Y 1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation
| العنوان: | Pharmacological inhibition of the F 1 -ATPase/P2Y 1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation |
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| المؤلفون: | Paula Honorato, Marcelo González, Cendrine Cabou, Laure Frayssinhes, Bernard Masri, Claudio Aguayo, Valeria Aguilera, Laurent O. Martinez, Thibaut Duparc, Audren Fournel, Marcelo León, Anne Abot, Claude Knauf, Claudia Radojkovic, Guillaume Combes, Luis Briceño, Nicol Parada, Lamia Ghezali |
| المساهمون: | Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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), Département de physiologie humaine [UNIV Paul Sabatier, Toulouse] (Faculté de Pharmacie), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Clinical Biochemistry and Immunology [Concepción, Chile] (Faculty of Pharmacy), Universidad de Concepción [Chile], Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Group of Research and Innovation in Vascular Health [Chillan, Chile] (GRIVAS Health), Vascular Physiology Laboratory [Concepción, Chile] (Department of Physiology), Universidad de Concepción [Chile]-Faculty of Biological Sciences [Concepción, Chile], Department of Obstetrics and Gynecology [Concepción, Chile] (Faculty of Medicine), This work was supported by the 'Fondo Nacional de Desarrollo Científico y Tecnológico' (FONDECYT, #11121575, Chile), 'Dirección de Investigación Universidad de Concepción' (DIUC, #210.072.033-1.0, Chile), the French National Research Agency (ANR, #ANR-16-CE18-0014-01, HDLNEXT-THERAPEUTICS) and the 'Région Midi-Pyrénées - Occitanie' (CLE 2015, #14054132). 'INNOVA BIO BIO Chile para Apoyo de Tesis' fellowships were held by P. Honorato (#13.1285-EM.TES) and M. León (#12.127-EM.TES). L. Briceño was supported by 'Comisión Nacional de Investigación Científica y Tecnológica CONICYT-PCHA/Magíster Nacional' (#2014-63566), Chile., ANR-16-CE18-0014,HDL-NEXT-THERAPEUTICS,Nouvelles thérapies du HDL-cholestérol pour les maladies cardiovasculaire.(2016), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), MARTINEZ, Laurent, Nouvelles thérapies du HDL-cholestérol pour les maladies cardiovasculaire. - - HDL-NEXT-THERAPEUTICS2016 - ANR-16-CE18-0014 - AAPG2016 - VALID, Faculté des Sciences Pharmaceutiques, Universidad de Concepción - University of Concepcion [Chile], Universidad de Concepción - University of Concepcion [Chile]-Faculty of Biological Sciences [Concepción, Chile] |
| المصدر: | Acta Physiologica Acta Physiologica, Wiley, 2019, 1, pp.e13268. ⟨10.1111/apha.13268⟩ Acta Physiologica, Wiley, 2019, 1 (3), pp.e13268. ⟨10.1111/apha.13268⟩ Acta Physiologica 3 (226), e13268. (2019) Acta Physiologica, 2019, 1 (3), pp.e13268. ⟨10.1111/apha.13268⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, P2Y receptor, Physiology, ATPase, Vasodilation, 030204 cardiovascular system & hematology, Pharmacology, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, nitric oxide, purinergic receptors, Receptor, Physiologie, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, F1-ATPase, Chemistry, Purinergic receptor, Apolipoprotein A1, endothelial cells, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adenosine diphosphate, 030104 developmental biology, biology.protein, lipids (amino acids, peptides, and proteins), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Autre (Sciences du Vivant), Lipoprotein |
| الوصف: | C. Radojkovic and L.O. Martinez are co-senior authors.; International audience; AIM:The contribution of apolipoprotein A1 (APOA1), the major apolipoprotein of high-density lipoprotein (HDL), to endothelium-dependent vasodilatation is unclear, and there is little information regarding endothelial receptors involved in this effect. Ecto-F1 -ATPase is a receptor for APOA1, and its activity in endothelial cells is coupled to adenosine diphosphate (ADP)-sensitive P2Y receptors (P2Y ADP receptors). Ecto-F1 -ATPase is involved in APOA1-mediated cell proliferation and HDL transcytosis. Here we investigated the effect of lipid-free APOA1 and the involvement of ecto-F1 -ATPase and P2Y ADP receptors on nitric oxide (NO) synthesis and the regulation of vascular tone.METHOD:NO synthesis was assessed in human endothelial cells from umbilical veins (HUVECs) and isolated mouse aortas. Changes in vascular tone were evaluated by isometric force measurements in isolated human umbilical and placental veins and by assessing femoral artery blood flow in conscious mice.RESULTS:Physiological concentrations of lipid-free APOA1 enhanced endothelial NO synthesis, which was abolished by inhibitors of endothelial nitric oxide synthase (eNOS) and of the ecto-F1 -ATPase/P2Y1 axis. Accordingly, APOA1 inhibited vasoconstriction induced by thromboxane A2 receptor agonist and increased femoral artery blood flow in mice. These effects were blunted by inhibitors of eNOS, ecto-F1 -ATPase and P2Y1 receptor.CONCLUSIONS:Using a pharmacological approach, we thus found that APOA1 promotes endothelial NO production and thereby controls vascular tone in a process that requires activation of the ecto-F1 -ATPase/P2Y1 pathway by APOA1. Pharmacological targeting of this pathway with respect to vascular diseases should be explored. This article is protected by copyright. All rights reserved. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1748-1708 1748-1716 |
| DOI: | 10.1111/apha.13268⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89721503e92f900cb14dd61aa841a880 https://www.hal.inserm.fr/inserm-02393118 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....89721503e92f900cb14dd61aa841a880 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17481708 17481716 |
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| DOI: | 10.1111/apha.13268⟩ |