Disturbed angiogenic activity in sera from obstructive sleep apnea patients

It is increasingly recognized that obstructive sleep apnea (OSA) syndrome is a systematic rather than local disorder. There is also growing evidence that apart from the syndrome's major features: intermittent hypoxia and sleep fragmentation, functional activity of the immune system is altered in OSA patients, with several cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) taking active part in sleep regulation. Little is known about the effects exerted by chronic intermittent hypoxia combined with persistent pro-inflammatory activity of the immune system on the vascular micro milieu in OSA. In this study we attempted to confirm the hypothesized imbalance between pro- and anti-angiogenic factors by evaluating direct and indirect angiogenic activity of OSA patients' sera in the in vivo serum-induced angiogenesis (SIA) and leukocyte-induced (LIA) assays, respectively, in mice. Both tests revealed significantly inhibited angiogenic activity of OSA patients' sera compared with healthy controls (P<0.001). Moreover, differences related to the subject's weight regarding in the mean number of newly-formed vessels were observed with a significantly greater inhibition in the normal-weighing apneic subjects than in the overweight or obese ones (P<0.01). The angiogenesis inhibition index was positively related to the serum IL-6 level (r=0.35; P<0.05) in the OSA group, but not to TNF-alpha, fasting serum leptin, or OSA syndrome severity as assessed by the AHI index. Our results demonstrate that OSA is accompanied by disturbed serum angiogenic activity, apparently resulting from an imbalance between pro- and anti-angiogenic factors, some of them being produced by the adipose tissue. The disordered angiogenic activity might be related to the pathophysiology of OSA and should be considered an important causative factor for the increased prevalence of cardiovascular diseases in OSA patients.