Aleksandra Franczak1,2, Robert Skomro3,4, Jolanta Sawicka5, Iwona Bil-Lula2, Andrhea Nocon1, Mark Fenton1,6, Joshua Lawson7,8, Grzegorz Sawicki9,10. 1. Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, Saskatchewan, S7N 0W8, Canada. 2. Department of Medical Laboratory Diagnostics, Wroclaw Medical University, Wroclaw, Poland. 3. Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, Saskatchewan, S7N 0W8, Canada. r.skomro@usask.ca. 4. Canadian Sleep and Circadian Network, Canada, Canada. r.skomro@usask.ca. 5. Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N 5E5, Canada. 6. Canadian Sleep and Circadian Network, Canada, Canada. 7. Canadian Centre for Health and Safety in Agriculture, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 8. Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 9. Department of Medical Laboratory Diagnostics, Wroclaw Medical University, Wroclaw, Poland. greg.sawicki@usask.ca. 10. Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N 5E5, Canada. greg.sawicki@usask.ca.
Abstract
PURPOSE: Intermittent hypoxia in obstructive sleep apnea (OSA) resembles ischemia/reperfusion. Oxidative stress during ischemia/reperfusion increases matrix metalloproteinase-2 (MMP-2) activity and leads to adverse cardiovascular consequences in animal models, but there is scarce information about MMP-2 in humans with OSA. The aim of this study was to determine if serum MMP-2 levels of patients with OSA differ from controls and if MMP-2 activity correlates with the severity of OSA and level of hypoxemia. METHODS: Patients with OSA (n = 124) were recruited from the Sleep Disorders Center (Saskatoon City Hospital, Canada) after in-lab polysomnography (PSG). Controls (n = 26) were subjects referred for PSG who did not have OSA. Severity of OSA was categorized according to American Academy of Sleep Medicine criteria. Level of hypoxemia was expressed as oxygen desaturation index (ODI; 3% desaturation). Gelatin zymography was performed to measure serum MMP-2 activity. RESULTS: Serum MMP-2 activity was significantly higher in patients with OSA than in controls (p = 0.029). MMP-2 activity in patients with severe OSA was significantly higher than in those with mild/moderate OSA and controls (p = 0.002). Linear regression showed positive associations with MMP-2 activity in serum for AHI (p < 0.001) and ODI (p = 0.003). The associations persisted after adjustment for multiple confounders, including age, sex, BMI, and cardiovascular disease. CONCLUSIONS: Serum MMP-2 activity was associated with OSA severity, and level of hypoxemia in patients with OSA, suggesting MMP-2 is worth considering as a potential biomarker to be included in future studies on sets of biomarkers for hypoxemic insult in OSA.
PURPOSE: Intermittent hypoxia in obstructive sleep apnea (OSA) resembles ischemia/reperfusion. Oxidative stress during ischemia/reperfusion increases matrix metalloproteinase-2 (MMP-2) activity and leads to adverse cardiovascular consequences in animal models, but there is scarce information about MMP-2 in humans with OSA. The aim of this study was to determine if serum MMP-2 levels of patients with OSA differ from controls and if MMP-2 activity correlates with the severity of OSA and level of hypoxemia. METHODS: Patients with OSA (n = 124) were recruited from the Sleep Disorders Center (Saskatoon City Hospital, Canada) after in-lab polysomnography (PSG). Controls (n = 26) were subjects referred for PSG who did not have OSA. Severity of OSA was categorized according to American Academy of Sleep Medicine criteria. Level of hypoxemia was expressed as oxygen desaturation index (ODI; 3% desaturation). Gelatin zymography was performed to measure serum MMP-2 activity. RESULTS: Serum MMP-2 activity was significantly higher in patients with OSA than in controls (p = 0.029). MMP-2 activity in patients with severe OSA was significantly higher than in those with mild/moderate OSA and controls (p = 0.002). Linear regression showed positive associations with MMP-2 activity in serum for AHI (p < 0.001) and ODI (p = 0.003). The associations persisted after adjustment for multiple confounders, including age, sex, BMI, and cardiovascular disease. CONCLUSIONS: Serum MMP-2 activity was associated with OSA severity, and level of hypoxemia in patients with OSA, suggesting MMP-2 is worth considering as a potential biomarker to be included in future studies on sets of biomarkers for hypoxemic insult in OSA.
Authors: Vishesh K Kapur; Dennis H Auckley; Susmita Chowdhuri; David C Kuhlmann; Reena Mehra; Kannan Ramar; Christopher G Harrod Journal: J Clin Sleep Med Date: 2017-03-15 Impact factor: 4.062
Authors: Aleksandra Franczak; Iwona Bil-Lula; Grzegorz Sawicki; Mark Fenton; Najib Ayas; Robert Skomro Journal: Sleep Med Rev Date: 2019-03-30 Impact factor: 11.609
Authors: Paul E Peppard; Terry Young; Jodi H Barnet; Mari Palta; Erika W Hagen; Khin Mae Hla Journal: Am J Epidemiol Date: 2013-04-14 Impact factor: 4.897
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