title: Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea.
abstract: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during transient cessation of breathing, triples the risk for cardiovascular diseases. We used a phage display peptide library as an unbiased approach to investigate whether IH, which is specific to OSA, activates endothelial cells (ECs) in a distinctive manner. The target of a differentially bound peptide on ECs collected from OSA patients was identified as CD59, a major complement inhibitor that protects ECs from the membrane attack complex (MAC). A decreased proportion of CD59 is located on the EC surface in OSA patients compared with controls, suggesting reduced protection against complement attack. In vitro, IH promoted endothelial inflammation predominantly via augmented internalization of CD59 and consequent MAC deposition. Increased internalization of endothelial CD59 in IH appeared to be cholesterol-dependent and was reversed by statins in a CD59-dependent manner. These studies suggest that reduced complement inhibition may mediate endothelial inflammation and increase vascular risk in OSA patients.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Memet
authors.initials: M
authors.lastname: Emin
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Castagna
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Josanna
authors.initials: J
authors.lastname: Rodriguez-Lopez
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Romina
authors.initials: R
authors.lastname: Wahab
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Tessa
authors.initials: T
authors.lastname: Adams
authors.affiliation: Division of Biostatistics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. sj366@cumc.columbia.edu.
authors.forename: Sanja
authors.initials: S
authors.lastname: Jelic
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D018957:CD59 Antigens / Q000378:metabolism*; D016022:Case-Control Studies; D061505:Cell Surface Display Techniques; D002784:Cholesterol / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000473:pathology*
chemical_list: D018957:CD59 Antigens; D015938:Complement Membrane Attack Complex; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008565:Membrane Proteins; D002784:Cholesterol