Research ArticleOBSTRUCTIVE SLEEP APNEA

Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea

Science Translational Medicine  06 Jan 2016:
Vol. 8, Issue 320, pp. 320ra1
DOI: 10.1126/scitranslmed.aad0634

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Sleep tight, don’t let the complement bite

Obstructive sleep apnea is a common medical condition characterized by intermittent cessation of breathing during sleep, which results in intermittent hypoxia. It greatly increases patients’ risk of cardiovascular disease, and now Emin et al. provide a mechanism, which helps to explain this correlation. The authors discovered that intermittent hypoxia causes internalization of CD59, a protein that is normally found on the membrane of endothelial cells and protects them from being injured by circulating complement. After internalization, CD59 could no longer protect the cells, resulting in damage to the vascular walls. In contrast, statins stabilized CD59 on the endothelial cell surface and protected them from injury, revealing yet another mechanism by which these versatile drugs protect against cardiovascular disease.

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.

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