Serum matrix metalloproteinase-2 as a predictor of level of hypoxemia and severity of obstructive sleep apnea
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SLEEP BREATHING PHYSIOLOGY AND DISORDERS • ORIGINAL ARTICLE
Serum matrix metalloproteinase-2 as a predictor of level of hypoxemia and severity of obstructive sleep apnea Aleksandra Franczak 1,2 & Robert Skomro 1,3 & Jolanta Sawicka 4 & Iwona Bil-Lula 2 & Andrhea Nocon 1 & Mark Fenton 1,3 & Joshua Lawson 5,6 & Grzegorz Sawicki 2,4 Received: 26 June 2020 / Revised: 12 September 2020 / Accepted: 17 September 2020 # Springer Nature Switzerland AG 2020
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. Keywords Obstructive sleep apnea . Sleep disordered breathing . Matrix metalloproteinase . Oxidative stress . Hypoxic burden
Introduction Obstructive sleep apnea (OSA) is the most common sleeprelated breathing disorder, affecting approximately 13% of adult men and 6% of adult women with the prevalence increasing with age [1]. Recurrent episodes of apnea/hypopnea
* Robert Skomro [email protected]
in OSA cause a desaturation-reoxygenation sequence. It resembles the ischemia/reperfusion phenomenon which is associated with excessive production of reactive oxygen species (ROS) [2] and an increase in matrix metalloproteinase (MMP) activity [3].
3
Canadian Sleep and Circadian Network, Canada, Canada
4
Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada
5
Canadian Centre for Hea
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