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BACKGROUND: Obesity is associated with an elevated risk for several types of cancer and thus a major health hazard. However, the mechanism between overweight and cancer susceptibility is still elusive. Leptin, mainly produced by adipocytes links food intake and energy expenditure. In addition, recent studies have shown an immunomodulatory impact of leptin on NK cells. The purpose of the present study was to investigate whether leptin stimulation of NK cells from obese humans leads to altered functions as compared to NK cells from lean subjects. On the basis of body mass index 20 healthy individuals were classified in two groups: normal weight (<25 kg/m(2)) and obese (>30 kg/m(2)). Peripheral blood mononuclear cells (PBMC) were isolated from blood samples. We used flow cytometry to assess differences in phenotype and activity markers (CD107a, CD178 and TRAIL) of PBMCs between both groups. Furthermore, we determined after short-term in vitro leptin stimulation the phosphorylation of JAK2, downstream target of the intracellular signaling cascade of the leptin receptor, by Western Blotting and numbers of NK-cell-tumor-cell-conjugates as well as Granzyme(+) and IFN-γ(+) NK cells by flow cytometry. Finally, the proliferative capacity of control and long-term (7 days) leptin-stimulated NK cells was examined. RESULTS: As opposed to similar NK cell counts, the number of CD3(+)CD56(+) cells was significantly lower in obese compared to lean subjects. Human NK cells express the leptin receptor (Ob-R). For further determination of Ob-R, intracellular target proteins of PBMCs were investigated by Western Blotting. Phosphorylation of JAK2 was lower in obese as compared to normal weight subjects. Furthermore, significantly lower levels of TNF-related apoptosis-inducing ligand (TRAIL) as an NK cell functional marker in obese subjects were found. In vitro leptin stimulation resulted in a higher production of interferon-γ in NK cells of normal weight subjects. Interestingly, long-term leptin stimulation had no significant influence on numbers of proliferating NK cells. CONCLUSIONS: NK cells from obese healthy humans show functional deficits and altered responses after in vitro leptin challenge.
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INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS), characterised by intermittent hypoxia/re-oxygenation, has been identified as an independent risk factor for cardiovascular diseases and endothelial dysfunction. Our aim was to investigate flow-mediated dilatation (FMD) in patients with obstructive sleep apnoea with and without metabolic syndrome. MATERIALS AND METHODS: Fifty-two subjects with OSAS diagnosed by polysomnography were classified into 2 groups according to the presence and absence of the metabolic syndrome and also according to the severity: mild to moderate OSAS group and severe OSAS group. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was assessed by establishing reactive hyperaemia and endothelial-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. Spearman correlation and regression analysis were performed. RESULTS: EDD was not significantly different in patients with OSAS and metabolic syndrome as compared with OSAS without metabolic syndrome (4.62 +/- 0.69 versus 4.49 +/- 0.93, P >0.05). CONCLUSIONS: Endothelial dysfunction in OSA may be independent of metabolic syndrome.
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Endotelio Vascular/fisiopatología , Síndrome Metabólico , Apnea Obstructiva del Sueño/complicaciones , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Endotelio Vascular/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ultrasonografía , Adulto JovenRESUMEN
Sleep apnea (SA) is more prevalent in patients with atrial fibrillation (AF), but the impact of cardioversion on disordered breathing is unknown. Thus, we investigated the influence of restoring sinus rhythm in patients with AF and atrial flutter (AFlut) on SA. The 16 patients (mean age 63.1 +/- 11.2) with AF (n = 6) or AFlut (n = 10) and SA (apnea-hypopnea index >10) received cardioversion or ablation of cavotricuspid isthmus. We compared the severity of SA by sleep polygraphy under AF/Aflut with the first night after restoring sinus rhythm and after 4 weeks. Apnea-hypopnea index before and immediately after restoring sinus rhythm was similar (31.7 +/- 13.2 vs 30.1 +/- 15.7, p = NS) despite a significantly reduced heart rate (86.7 +/- 26.5 vs 67.8 +/- 11.9 beats/min, p <0.02). After 4 weeks, apnea-hypopnea index remained unchanged (38.1 +/- 18.1, p = NS) although heart rate was further reduced (61.8 +/- 8.8 beats/min, p <0.003). In our study, SA could not be improved by cardioversion of AF/AFlut. Therefore, although it is well known that SA leads to AF, eliminating AF does not cure or improve SA. In conclusion, our study shows that AF should be regarded more as an innocent bystander than a causative or aggravating condition in SA.