Lectin-like oxidized low-density lipoprotein receptor-1 modulates endothelial apoptosis in obstructive sleep apnea

Chest. 2011 Dec;140(6):1503-1510. doi: 10.1378/chest.11-0302. Epub 2011 May 12.

Abstract

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(1)) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Apoptosis / physiology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Continuous Positive Airway Pressure / methods*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polysomnography / methods
  • Prospective Studies
  • Reference Values
  • Scavenger Receptors, Class E / metabolism*
  • Severity of Illness Index
  • Sleep Apnea, Obstructive / blood*
  • Sleep Apnea, Obstructive / diagnosis
  • Sleep Apnea, Obstructive / therapy*

Substances

  • Biomarkers
  • Scavenger Receptors, Class E