doi: 10.1111/j.1365-2869.2009.00789.x Heat-shock protein 70: expression in monocytes of patients with sleep apnoea and association with oxidative stress and tumour necrosis factor-a LENA LAVIE, LARISSA DYUGOVSKAYA, ORIT GOLAN-SHANY and PERETZ LAVIE Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Accepted in revised form 13 August 2009; received 28 November 2008 SUMMARY Obstructive sleep apnoea (OSA) is associated with a variety of nightly stresses, including intermittent hypoxaemia, oxidative stress and sleep fragmentation. Heat- shock proteins (HSPs) are upregulated in response to an array of environmental and metabolic stresses. We hypothesized that the OSA-related stresses would affect the expression of HSP70 in monocytes. Basal (30 min, at 37 °C), heat stress-induced HSP70 (30 min, at 43 °C) and basal tumour necrosis factor-a (TNF-a) were determined by flow cytometry in monocytes of 10 patients with OSA and 10 controls matched by age, gender and body mass index. Oxidative stress was determined by thiobarbituric acid- reactive substances (TBARS) and antioxidant paraoxonase-1 activity. Basal HSP70 expression was 1.8-fold higher in patients with OSA as compared with controls (P < 0.0005) and was significantly positively correlated with TBARS (r = 0.56, P < 0.009). However, induction of HSP70 in response to heat stress treatment was lower by 40% in OSA monocytes as compared with controls (P < 0.0003). Further- more, heat stress-induced HSP70 expression was significantly negatively correlated with basal HSP70 expression independently of apnoea severity (r = )0.69, P < 0.0006). Also, basal intracellular TNF-a expression was inversely correlated with heat-shock- induced HSP70 (r = )0.78, P < 0.015) in OSA monocytes but not in controls. In conclusion, basal HSP70 overexpression that is a protective mechanism indicative of disease-associated stress was significantly higher in patients with OSA and was correlated with oxidative stress. On the other hand, in response to a defined heat-stress treatment, the induction of HSP70 was lower in patients with OSA, indicative of a possible maladaptive response to an acute stress. Correlations with oxidative stress and TNF-a further support this conclusion. keywords heat-shock protein 70, monocytes, oxidative stress, sleep apnoea INTRODUCTION Obstructive sleep apnoea (OSA) is characterized by a cyclic occurrence of apnoeic events during sleep that are associated with intermittent hypoxaemia and terminated by brief electro- encephalographic and autonomic arousals (Malhotra and White, 2002). A large body of evidence demonstrates an association between OSA and cardiovascular morbidity, particularly with hypertension (Quan and Gersh, 2004; Shamsuzzaman et al., 2003). Although the underlying mech- anisms are not fully elucidated, cumulative evidence indicates that oxidative stress (Lavie, 2003, 2005; Suzuki et al., 2006) and activated inflammatory cells play a major role in this association (Dyugovskaya et al., 2002, 2003, 2005a,b). Correspondence: Dr Lena Lavie, Unit of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, POB 9649, 31096, Haifa, Israel. Tel.: +972 4 8295234; fax: +972 4 8295403 or +972 4 8343934; e-mail: lenal@tx.technion.ac.il J. Sleep Res. (2010) 19, 139–147 Breathing disorders in sleep Ó 2009 European Sleep Research Society 139