title: Coenzyme Q10 protects human endothelial cells from β-amyloid uptake and oxidative stress-induced injury.
abstract: Neuropathological symptoms of Alzheimer's disease appear in advances stages, once neuronal damage arises. Nevertheless, recent studies demonstrate that in early asymptomatic stages, ß-amyloid peptide damages the cerebral microvasculature through mechanisms that involve an increase in reactive oxygen species and calcium, which induces necrosis and apoptosis of endothelial cells, leading to cerebrovascular dysfunction. The goal of our work is to study the potential preventive effect of the lipophilic antioxidant coenzyme Q (CoQ) against ß-amyloid-induced damage on human endothelial cells. We analyzed the protective effect of CoQ against Aβ-induced injury in human umbilical vein endothelial cells (HUVECs) using fluorescence and confocal microscopy, biochemical techniques and RMN-based metabolomics. Our results show that CoQ pretreatment of HUVECs delayed Aβ incorporation into the plasma membrane and mitochondria. Moreover, CoQ reduced the influx of extracellular Ca(2+), and Ca(2+) release from mitochondria due to opening the mitochondrial transition pore after β-amyloid administration, in addition to decreasing O2(.-) and H2O2 levels. Pretreatment with CoQ also prevented ß-amyloid-induced HUVECs necrosis and apoptosis, restored their ability to proliferate, migrate and form tube-like structures in vitro, which is mirrored by a restoration of the cell metabolic profile to control levels. CoQ protected endothelial cells from Aβ-induced injury at physiological concentrations in human plasma after oral CoQ supplementation and thus could be a promising molecule to protect endothelial cells against amyloid angiopathy.
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Castilla-la Mancha, Ciudad Real, Spain; Oxidative Stress and Neurodegeneration Group, Regional Centre for Biomedical Research, Ciudad Real, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Durán-Prado
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Castilla-la Mancha, Ciudad Real, Spain; Oxidative Stress and Neurodegeneration Group, Regional Centre for Biomedical Research, Ciudad Real, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Frontiñán
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Castilla-la Mancha, Ciudad Real, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Santiago-Mora
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Castilla-la Mancha, Ciudad Real, Spain; Oxidative Stress and Neurodegeneration Group, Regional Centre for Biomedical Research, Ciudad Real, Spain.
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Peinado
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Castilla-la Mancha, Ciudad Real, Spain; Oxidative Stress and Neurodegeneration Group, Regional Centre for Biomedical Research, Ciudad Real, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Parrado-Fernández
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies and Instituto Regional de Investigación Científica Aplicada, Universidad de Castilla-La Mancha, Ciudad Real, Spain; Fundación Parque Científico y Tecnológico de Albacete, Albacete, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Gómez-Almagro
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies and Instituto Regional de Investigación Científica Aplicada, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Faculty of Sciences, University of Córdoba, Agrifood Campus of International Excellence ceiA3, Córdoba, Spain.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: López-Domínguez
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Faculty of Sciences, University of Córdoba, Agrifood Campus of International Excellence ceiA3, Córdoba, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Villalba
authors.affiliation: Department of Medical Sciences, Faculty of Medicine, University of Castilla-la Mancha, Ciudad Real, Spain; Oxidative Stress and Neurodegeneration Group, Regional Centre for Biomedical Research, Ciudad Real, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alcaín
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018384:Oxidative Stress; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D014451:Ubiquinone; C024989:coenzyme Q10