Circulating plasma levels of vascular endothelial growth factor in patients with sleep disordered breathing

Department of Respiratory and Critical Care Medicine Otto-Wagner-Spital, Vienna, Austria.
Respiratory Medicine (Impact Factor: 3.09). 01/2005; 98(12):1180-6. DOI: 10.1016/j.rmed.2004.04.009
Source: PubMed


Cellular vascular endothelial growth factor (VEGF) expression is increased in response to regional hypoxia, however, contradictory results were reported on the effects of systemic hypoxemia on circulating VEGF levels. This study investigated plasma concentrations of VEGF in patients with a variable degree of overnight hypoxemia due to sleep disordered breathing (SDB).
VEGF levels were assessed by ELISA in non-activated (VEGFbl) and thrombin stimulated platelet rich plasma (VEGFprp) of 45 patients with SDB: Group 1 patients with obstructive sleep apnea and an apnea-hypopnea index (AHI) > 15/h; Group 2 subjects with an AHI < 5/h; Group 3 patients on CPAP treatment for sleep apnea.
39 patients were included in the final analysis. Patients in Group 1 had a higher %time of sleep with SaO2 <90% and a significantly lower mean and minimum overnight oxygen saturation than subjects in Group 2 and patients in Group 3 (P<0.05). Despite significant differences in overnight oxygenation, VEGFbl and VEGFprp concentrations were not significantly different between the three study groups. However, plasma levels of VEGFbl were significantly higher (P = 0.02) in SDB patients with arterial hypertension (n = 19; VEGFbl: 14.0+/-3.3 pg/ml) than in those without arterial hypertension (n = 20; VEGFbl: 10.9+/-5.2 pg/ml). There were no relationships between VEGF levels and polysomnographic oxygenation parameters. In univariate analysis we observed significant relationships for VEGFbl with BMI (C: 0.393; P<0.05) and serum fibrinogen (C: 0.399; P<0.05).
Circulating plasma VEGF levels in patients with sleep disordered breathing may be unrelated to night time hypoxemia (257 Words).

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    • "Vascular endothelial growth factor (VEGF) plays a significant role in angiogenesis and endothelial function [5], [6]. It is primarily regulated via hypoxia-inducible factor-1α (HIF-1α) in response to hypoxia and its circulating level is increased in patients with OSA [7]. We have previously shown that hypertensive OSA patients have increased circulating levels of VEGF receptor-1 also known as sFlt-1 compared to normotensive counterparts [8]. "
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    ABSTRACT: Purpose Obstructive sleep apnea (OSA) is a common disorder affecting 15–24% of the adults and is associated with increased risk of hypertension and atherosclerosis. The exact mechanisms underlying hypertension in OSA are not entirely clear. YKL-40/Chitinase-3-like protein-1 is a circulating moiety with roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis and a number of other diseases. We sought to determine the role of YKL-40 in endothelial dysfunction and hypertension in OSA. Methods We studies 23 normotensive OSA (N-OSA) and 14 hypertensive OSA (H-OSA) without diabetes and apparent cardiovascular disease. Endothelial-dependent nitric oxide-mediated vasodilatory capacity was assessed by flow-mediated vasodilation (FMD). YKL-40, vascular endothelial growth factor (VEGF) and the soluble form of VEGF receptor-1or sFlt-1 were measured in plasma using ELISA methodology. Results N-OSA subjects aged 49.1±2.3 years and H-OSA aged 51.3±1.9 years with BMI 36.1±1.6 and 37.6±1.9 kg/m2, respectively. The apnea-hypopnea index (AHI) was 41±5 events/hr in N-OSA and 46±6 in H-OSA with comparable degree of oxygen desaturations during sleep. FMD was markedly impaired in H-OSA (8.3%±0.8) compared to N-OSA (13.2%±0.6, P<0.0001). Plasma YKL-40 was significantly elevated in H-OSA (55.2±7.9 ng/ml vs. 35.6±4.2 ng/ml in N-OSA, P = 0.02) and had an inverse relationship with FMD (r = −0.52, P = 0.013). There was a significant positive correlation between sFlt-1/VEGF, a measure of decreased VEGF availability, and YKL-40 (r = 0.42, P = 0.04). Conclusion The levels of plasma YKL-40 were elevated in H-OSA group and inversely correlated with the endothelial-dependent vasodilatory capacity whereas there was a positive correlation between sFlt-1/VEGF and YKL-40. These findings suggest that YKL-40 is dysregulated, in part, due to perturbation of VEGF signaling, and may contribute to endothelial dysfunction and hypertension in OSA.
    PLoS ONE 05/2014; 9(5):e98629. DOI:10.1371/journal.pone.0098629 · 3.23 Impact Factor
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    • "age-dependent increase in systemic levels of VEGF in OSAS patients (Valipour et al. 2004; Peled et al. 2007). "
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    ABSTRACT: Obstructive sleep apnea syndrome (OSAS) is associated with recurrent nocturnal hypoxia during sleep; this hypoxia has been implicated in the pathogenesis of cardiovascular complication. However, a useful soluble factor that is sensitively correlated with OSAS severity for the diagnosis remains unidentified. We hypothesized that systemic levels of basic fibroblast growth factor (bFGF), a hypoxia-induced cytokine, were affected by nocturnal hypoxemia in OSAS patients, and we assessed whether the degree of change in the plasma bFGF concentrations before and after nocturnal hypoxia is correlated with the severity of OSAS. Thirty subjects who had suspected OSAS and had been investigated by nocturnal polysomnography (PSG) were enrolled. Plasma bFGF and vascular endothelial growth factor (VEGF) concentrations the night before PSG and the next morning were measured by sandwich enzyme-linked immunosorbent assay. Correlations between the changes in these factors and hypoxia-associated parameters for OSAS severity were analyzed. Patients with OSAS had significantly elevated levels of plasma bFGF but not VEGF and hemoglobin after rising. The degree of change in bFGF concentrations after nocturnal apnea episodes was significantly correlated with diagnostic parameters for OSAS severity. The change in plasma bFGF levels is associated with the degree of hypoxic state in OSAS patients, implying that bFGF might be a useful soluble factor for evaluating OSAS severity.
    SpringerPlus 12/2013; 2(1):260. DOI:10.1186/2193-1801-2-260
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    • "In patients with obstructive sleep apnoea (OSA) and animal models, intermittent hypoxia during sleep was associated with metabolic disturbances, such as decreased insulin sensitivity, increased serum lipids, and leptin resistance (Bonsignore & Eckel, 2009; Bonsignore et al., 2012; Jun & Polotsky, 2009). As for plasma VEGF, increased or stable plasma leptin levels have been reported in OSA patients (Kaditis et al., 2006; Lavie et al., 2002; Valipour et al., 2004). We hypothesized that nocturnal hypoxemia might affect morning baseline measurements of leptin and VEGF, and that maximal exercise at HA might affect leptin and VEGF levels. "
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    ABSTRACT: Context: High altitude (HA) is a model of severe hypoxia exposure in humans. We hypothesized that nocturnal hypoxemia or acute maximal exercise at HA might affect plasma leptin and VEGF levels. Objectives: Plasma leptin, VEGF and other metabolic variables were studied after nocturnal pulse oximetry and after maximal exercise in healthy lowlanders on the 3rd-4th day of stay in Lobuche (5050 m, HA) and after return to sea level (SL). Results: Leptin was similar at SL or HA in both pre- and post-exercise conditions. Pre-exercise VEGF at HA was lower, and cortisol was higher, than at SL, suggesting that nocturnal intermittent hypoxia associated with periodic breathing at HA might affect these variables. Conclusions: Leptin levels appear unaffected at HA, whereas nocturnal hypoxic stress may affect plasma VEGF. Future HA studies should investigate the possible role of nocturnal intermittent hypoxemia on metabolism.
    Archives of Physiology and Biochemistry 07/2013; 119(5). DOI:10.3109/13813455.2013.814679 · 1.76 Impact Factor
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