Statins reduced complement-related vascular inflammation in patients with obstructive sleep apnea, according to research published online Jan. 6 in Science Translational Medicine.
The “unexpected” finding suggests that statins might offer a targeted therapy for the significant vascular manifestations of OSA, wrote Dr. Memet Emin and Dr. Gang Wang of Columbia University College of Physicians and Surgeons, New York, together with their associates. “Statins also have antioxidant effects, which may be particularly beneficial in conditions associated with oxidative stress, such as OSA,” the investigators added.
Obstructive sleep apnoea affects one in four Western adults and triples the risk of cardiovascular diseases. The disorder is uniquely characterized by intermittent hypoxia, which the researchers hypothesized might lead to a distinct pattern of endothelial cell (EC) activation. To test this theory, they used a phage display peptide library to analyse protein expression in vascular ECs from 76 patients with OSA and 52 OSA-free controls. They also modelled intermittent hypoxia by exposing cultured ECs to alternating periods of normal and low (2%) oxygen levels (Sci Transl Med. 2016 Jan 6. doi: 10.1126/scitranslmed.aad0634).
Patients with OSA who were receiving statins had EC surface levels of the CD59 complement inhibitor similar to those of controls, and significantly greater levels compared with patients with OSA who were not receiving statins (P = .05). The CD59 protein is a major complement regulator that inhibits the formation of the terminal membrane attack complex, and thereby protects cells from complement-mediated injury, the researchers noted. In addition, intermittent hypoxia induced the internalization of CD59 in cultured ECs, leading to MAC deposition and endothelial inflammation, they said.
Most notably, patients with OSA who were taking statins had normal EC surface levels of CD59, and cultured ECs that were treated with atorvastatin were better protected from complement activity in a cholesterol-dependent manner, the investigators reported. By reducing cholesterol biosynthesis, statins might decrease the formation of cholesterol-enriched plasma membrane and CD59 endocytosis, which would reduce its internalization and preserve its ability to protect cells against complement activity, they said.
The National Heart, Lung, and Blood Institute of the National Institutes of Health funded the study. The investigators had no disclosures
Journal Reference
Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea
Memet Emin, Gang Wang1, Francesco Castagna, Josanna Rodriguez-Lopez, Romina Wahab, Jing Wang, Tessa Adams, Ying Wei and Sanja Jelic,Science Translational Medicine 06 Jan 2016:
Vol. 8, Issue 320, pp. 320ra1. DOI: 10.1126/scitranslmed.aad0634
