Pharmacological inhibition of the F1‐ATPase/P2Y1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation

• DOI: 10.1111/apha.13268
• Publication Date: 2019-03-01T10:40:10Z
• Authors: Cendrine Cabou; Paula Honorato; Luis Briceño; Lamia Ghezali; Thibaut Duparc; Marcelo León; Guillaume Combes; Laure Frayssinhes; Audren Fournel; Anne Abot; Bernard Masri; Nicol Parada; Valeria Aguilera; Claudio Aguayo; Claude Knauf; Marcelo González; Claudia Radojkovic; Laurent O. Martinez
• Keywords: Male; 0301 basic medicine; Nitric Oxide Synthase Type III; 610; Nitric Oxide; Mice; Receptors, Purinergic P2Y1; 03 medical and health sciences; [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system; nitric oxide; Pregnancy; 616; purinergic receptors; Human Umbilical Vein Endothelial Cells; Animals; Humans; Endothelium; Physiologie; F1-ATPase; Apolipoprotein A-I; Apolipoprotein A1; F1-ATPase;purinergic receptors;endothelial cells;nitric oxide; endothelial cells; Adenosine Diphosphate; Mice, Inbred C57BL; Vasodilation; Proton-Translocating ATPases; physiology; Apolipoprotein A1; Female; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Autre (Sciences du Vivant); Signal Transduction

The contribution of apolipoprotein A1 (APOA1), the major high-density lipoprotein (HDL), to endothelium-dependent vasodilatation is unclear, and there little information regarding endothelial receptors involved in this effect. Ecto-F1 -ATPase a receptor for APOA1, its activity cells coupled adenosine diphosphate (ADP)-sensitive P2Y (P2Y ADP receptors). APOA1-mediated cell proliferation HDL transcytosis. Here, we investigated effect lipid-free APOA1 involvement ecto-F1 on nitric oxide (NO) synthesis regulation vascular tone.Nitric was assessed human from umbilical veins (HUVECs) isolated mouse aortas. Changes tone were evaluated by isometric force measurements placental assessing femoral artery blood flow conscious mice.Physiological concentrations enhanced NO synthesis, which abolished inhibitors synthase (eNOS) -ATPase/P2Y1 axis. Accordingly, inhibited vasoconstriction induced thromboxane A2 agonist increased mice. These effects blunted eNOS, P2Y1 receptor.Using pharmacological approach, thus found that promotes production thereby controls process requires activation pathway APOA1. Pharmacological targeting with respect diseases should be explored.