Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Modulates Endothelial Apoptosis in Obstructive Sleep Apnea

Background: Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is the major receptor for oxidized low-density lipoprotein in endothelial cells, and its expression is enhanced in proatherogenic settings. The objective of this study was to investigate the association between LOX-1 in freshly harvested human venous endothelial cells and apoptotic circulating endothelial cells in patients with obstructive sleep apnea (OSA). Methods: We conducted a prospective, interventional study of 38 patients with newly diagnosed OSA free of disease and 12 healthy control subjects. Plasma LOX-1 (pLOX-1) levels were measured using a commercially available enzyme-linked immunosorbent assay. Protein expression of LOX-1 was quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 8 weeks of continuous positive airway pressure (CPAP) therapy. Circulating apoptotic endothelial cells (CD146(+), CD45(-), and CD31(+)) were assessed concomitantly by flow cytometry. Results: pLOX-1 levels were higher in subjects with OSA than in control subjects (326.9 +/- 267.1 pg/mL and 141.1 +/- 138.6 g/mL, respectively; P = .004). Patients with OSA showed a threefold increase in baseline endothelial expression of LOX-1 relative to control subjects. CPAP therapy resulted in a significant decrease in endothelial LOX-1 expression only in CPAP-adherent patients. Circulating apoptotic endothelial cells correlated directly with baseline expression of LOX-1 (R(2) = 0.32, P = .01) after adjustment for age, BMI, and waist to hip ratio. Conclusions: Increased expression of LOX-1 in vivo is associated with endothelial apoptosis. Adherence to CPAP therapy may reverse these derangements. CHEST 2011; 140(6):1503-1510