Lysyl Oxidase as a Serum Biomarker of Liver Fibrosis in Patients with Severe Obesity and Obstructive Sleep Apnea

Author(s):Show less -

Mesarwi, Omar A. ^[1] ; Shin, Mi-Kyung ^[1] ; Drager, Luciano F. ^[2] ; Bevans-Fonti, Shannon ^[1] ; Jun, Jonathan C. ^[1] ; Putcha, Nirupama ^[1] ; Torbenson, Michael S. ^[3] ; Pedrosa, Rodrigo P. ^[4] ; Lorenzi-Filho, Geraldo ^[4] ; Steele, Kimberley E. ^[5] ; Schweitzer, Michael A. ^[5] ; Magnuson, Thomas H. ^[5] ; Lidor, Anne O. ^[5] ; Schwartz, Alan R. ^[1] ; Polotsky, Vsevolod Y. ^[1]

Affiliation

^[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 - USA

^[2] Univ Sao Paulo, Sch Med, Hypertens Unit, Heart Inst InCor, Sao Paulo - Brazil

^[3] Mayo Clin, Div Anat Pathol, Rochester, MN - USA

^[4] Univ Sao Paulo, Sch Med, Sleep Lab, Div Pulm, Sao Paulo - Brazil

^[5] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 - USA

• Document type: Journal article
• Source: Sleep; v. 38, n. 10, p. 1583-U84, OCT 1 2015.
• Web of Science Citations: 20

Abstract

Study Objectives: Obstructive sleep apnea (OSA) is associated with the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that the hypoxia of OSA increases hepatic production of lysyl oxidase (LOX), an enzyme that cross-links collagen, and that LOX may serve as a biomarker of hepatic fibrosis. Design: Thirty-five patients with severe obesity underwent liver biopsy, polysomnography, and serum LOX testing. A separate group with severe OSA had serum LOX measured before and after 3 mo of CPAP or no therapy, as did age-matched controls. LOX expression and secretion were measured in mouse hepatocytes following exposure to hypoxia. Setting: The Johns Hopkins Bayview Sleep Disorders Center, and the Hypertension Unit of the Heart Institute at the University of Sao Paulo Medical School. Measurements and Results: In the bariatric cohort, the apnea-hypopnea index was higher in patients with hepatic fibrosis than in those without fibrosis (42.7 +/- 30.2 events/h, versus 16.2 +/- 15.5 events/h; P = 0.002), as was serum LOX (84.64 +/- 29.71 ng/mL, versus 45.46 +/- 17.16 ng/mL; P < 0.001). In the sleep clinic sample, patients with severe OSA had higher baseline LOX than healthy controls (70.75 ng/mL versus 52.36 ng/mL, P = 0.046), and serum LOX decreased in patients with OSA on CPAP (mean decrease 20.49 ng/mL) but not in untreated patients (mean decrease 0.19 ng/mL). Hypoxic mouse hepatocytes demonstrated 5.9-fold increased LOX transcription (P = 0.046), and enhanced LOX protein secretion. Conclusions: The hypoxic stress of obstructive sleep apnea may increase circulating lysyl oxidase (LOX) levels. LOX may serve as a biomarker of liver fibrosis in patients with severe obesity and nonalcoholic fatty liver disease. (AU)

• FAPESP's process: 12/02953-2 - Impact of obstructive sleep apnea and sleep duration on the progression of cardiovascular diseases
• Grantee: Luciano Ferreira Drager
• Support Opportunities: Research Grants - Young Investigators Grants