Differences in Overexpression of Hypoxia-induced Transcription Factors and Associated Biomarkers in Three Different Types of Chronic Hypoxia

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=> array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diferencias en la sobreexpresión de biomarcadores asociados a la hipoxia en tres tipos de hipoxia diferentes" ] ] "textoCompleto" => "Research into the impact of hypoxia has focused on chronic continuous hypoxia (CCH), characteristic of COPD<a class="elsevierStyleCrossRef" href="#bib0055">1</a> and chronic intermittent hypoxia (CIH), characteristic of sleep apnea–hypopnea syndrome (OSA).<a class="elsevierStyleCrossRefs" href="#bib0060">2,3</a> The co-existence of CCH and CIH results in a third type of hypoxia, “Overlap Syndrome”.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> The mechanisms of adaptation to these different types of hypoxia may be different, with changes on the cardiovascular system or the peripheral musculature, with a dose-response associated with hypoxia.<a class="elsevierStyleCrossRef" href="#bib0075">5</a>We hypothesized that the three models of hypoxia behave differently in the expression of hypoxia-induced transcription factors (factor inducible hypoxia 1–2 and factor nuclear Kappa-B,NF-KB), as well as inflammatory biomarkers including tumor necrosis factor α (TNF-α), interleukin (IL)-8, IL-6, vascular endothelial growth factor (VEGF), vascular cell adhesion protein 1 (VCAM-1), and biomarkers of oxidative stress including superoxide dismutase (SOD) and catalase activities (CAT), both systemically and in the peripheral muscle. Our objective was to compare the mechanisms of adaptation in patients with three types of hypoxia, on the expression of transcription factors sensitive to hypoxia, the expression of systemic inflammation, oxidative stress level and antioxidant capacity, at the systemic and at the muscle levels.This prospective, observational, cross-sectional study was conducted in male patients over 18 years, diagnosed with COPD, OSA or Overlap Syndrome, further a control group. All subjects underwent a clinical evaluation, spirometry with bronchodilator testing and a home respiratory polygraphy (Embletta Gold PG System).The COPD patients had FEV1<80% in post-bronchodilator spirometry, a daytime arterial partial pressure of oxygen (PaO2)<70mmHg and an apnea–hypopnea index (AHI)<5. The OSA patients had FEV1>80%, a PaO2>80mmHg, an AHI>15 and had not received CPAP treatment previously. The overlap group had FEV1<80%, a PaO2<70mmHg and an AHI>15. The control group had a normal spirometry with an AHI<5.Blood samples were collected by venipuncture and were immediately centrifuged, and plasma aliquots were stored at −80°C. Muscle biopsy samples were obtained from all patients (not in control group) from the vast lateral of the quadriceps muscle, frozen in liquid nitrogen and preserved at −80°C. For the analysis in plasma, we selected hypoxia-associated transcription factors, inflammatory, oxidative stress and antioxidants biomarkers. In the muscle biopsies we analyzed the gene expression of the inflammatory markers using reverse transcription quantitative polymerase chain reaction (RT-qPCR).The study included 34 subjects: 4 with COPD, 12 with OSA, 13 with overlap and 5 controls.The plasma concentration of transcription factors, inflammation and oxidative stress markers presented significant differences in the three groups of patients compared to the controls (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In plasma, the NF-KB1 was higher and SOD was significantly decreased in the OSA group compared with COPD and Overlap Syndrome.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>As regards the muscle gene expression of transcription factors (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), we found that in COPD patients the expression of VCAM-1 was higher and SOD was lower than in OSA and overlap groups.In the OSA group we found a significant correlation (r=0.579; P=.04) between the levels of NF-KB1 obtained in plasma and in muscle, besides a significant correlation between the inflammatory and oxidative biomarkers in plasma and in muscle: plasma IL8-muscle SOD (r=0.69; P=.01); plasma endothelin-muscle CAT (r=0.61; P=.03); plasma ICAM-muscle IL8 (r=0.71; P=.009) and plasma ICAM-muscle CAT (r=0.80; P=.002).In COPD group there was an increase in muscle expression of VCAM-1 compared to OSA, and a decreased in SOD compared with the other two groups.The three groups of hypoxemic patients show an overexpression of hypoxia-sensitive transcription factors, primarily HIF-1α, compared to control subjects. In OSA there was an increase in plasma levels of NF-κB1 compared to COPD group. In situations of CIH, overexpression of NF-κB1 in plasma has been demonstrated in a cell culture model<a class="elsevierStyleCrossRef" href="#bib0080">6</a> with a selective activation of inflammatory pathways, unlike CCH hypoxia of patients with COPD and overlap, where the activation of adaptive pathways predominates. Oxidative stress driven by CIH may initiate systemic inflammation in OSA,<a class="elsevierStyleCrossRef" href="#bib0085">7</a> which inflammatory response in turn promoting the development of cardiovascular morbidities.<a class="elsevierStyleCrossRefs" href="#bib0090">8,9</a> We have found a decrease in the plasma of SOD in OSA patients. In situations with a chronically oxidative stress due to overexpression of NF-κB1, there may be a decrease in SOD by a saturation of the antioxidant systems.We found no differences between the three patient groups in the expression of transcription factors in peripheral musculature. However, in COPD there is a higher level of VCAM and lower SOD than in OSA, reflecting a more intense inflammatory state at the muscle, besides a lower ability to nullify the deleterious effect of free radicals. These findings match with the findings of other authors<a class="elsevierStyleCrossRef" href="#bib0100">10</a> and agree with that muscle dysfunction in COPD is clinically important. In patients with CCH, inflammatory and oxidative processes in plasma and in muscle fiber seem to be independent. In OSA, there is a correlation between the levels of the NF-KB in plasma and in muscle fiber, as well as between parameters of inflammatory and antioxidant status in plasma and peripheral muscle, suggesting that inflammation and oxidative stress at the systemic levels and in the muscle are interrelated processes.In summary, the three groups of hypoxemic patients show an overexpression of hypoxia-sensitive transcription factors, with a higher expression of NF-κB in OSA. In plasma, an increase in oxidative stress is evident in the three groups, but the deficit in antioxidant substances is greater in OSA, which may be due to the overexpression of NF-κB. At peripheral muscle, there were no differences in inflammatory parameters, unlike the response to oxidative stress, with an increase in the production of free radicals and a decrease in antioxidant substances in COPD patients versus OSA patients. Inflammation and oxidative stress in plasma and muscle in COPD and COPD-OSA seem to be independent phenomena. In OSA, inflammatory and oxidative stress levels in muscle fiber are related to systemic levels.Funding SourceGrants for projects of the Association of Pulmonologists of the South. Neumosur. Project: Expression of transcription factors sensitive to hypoxia, inflammatory response and oxidative stress at the systemic and muscular level in three clinical models of hypoxemia.Research grants 2012 SEPAR. Code: 051|2012. Expression of transcription factors sensitive to hypoxia, the inflammatory response, oxidative stress and peripheral muscle involvement in three clinical models of hypoxemia.Conflicts of InterestNone declared." "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding Source" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of Interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviations: COPD: chronic obstructive pulmonary disease; OSA: sleep apnea–hypopnea syndrome; HIF-1α: hypoxia inducible factor 1, subunit α; HIF-2α: hypoxia inducible factor 2, subunit α; NF-κB1: nuclear factor kappa-B 1; IL- 6: interleukin-6; IL- 8: interleukin-8; TNF-α: tumor necrosis factor alpha; VEGF: vascular endothelial growth factor; VCAM-1: vascular cell adhesion protein 1; CAT: catalase activity; SOD: superoxide dismutase activity." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Plasma Biomarkers \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OSA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overlap \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIF-1α (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">254.8±83.6<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">210.2±124.8<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">178.2±157.1<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.8±35.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIF-2α (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3±3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.7±29.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.8±29.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.7±8.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NF-κB1 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.5±2.6† \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.8±4.3<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.2±6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.8±3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-6 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.1±1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.6±1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9±0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-8 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.1±0.4<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.2±1.6<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.2±0.7<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2±1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-α (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6±0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.5±0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.7±0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.5±0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VEGF (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.6±53.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.7±29.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.2±47.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.1±55.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VCAM-1 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42.4±39.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.5±21.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.9±25.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5±10.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CAT (nmol/min/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80.2±30.3<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.9±25.4<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.5±14.5<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.0±1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SOD (U/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3±0.1<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">†</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0±0.2<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">†</a>,<a class="elsevierStyleCrossRef" href="#tblfn0015">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3±0.5<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">†</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5±0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2667199.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Muscle biomarkers \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OSA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overlap \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIF-1α (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.052±0.078 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.05±0.034 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.058±0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIF-2α (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.13±0.157 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17±0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.33±6.72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NF-κB1 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.38±0.733 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.065±0.062 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.062±0.049 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-6 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007±0.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007±0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006±0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-8 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.022±0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.463±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.372±0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-α (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.03±0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002±0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005±0.009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VEGF (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.165±0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.126±0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.218±0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VCAM-1 (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.105±0.03<a class="elsevierStyleCrossRef" href="#tblfn0010">†</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.05±0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09±0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CAT (nmol/min/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.432±2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.733±0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.295±1.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SOD (U/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.577±3.6<a class="elsevierStyleCrossRef" href="#tblfn0010">†</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.856±9.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.954±17.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2667200.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "Significant differences (p<0.05) versus controls." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "†" "nota" => "Significant differences (p<0.05) versus SAHS." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "‡" "nota" => "Significant differences (p<0.05) versus overlap." ] ] ] "descripcion" => array:1 [ "en" => "Plasma Concentration of Transcription Factors, Inflammation and Oxidative Stress Markers, and Muscle Gene Expression of Transcription Factors, Inflammation and Oxidative Stress Parameters." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical differences in COPD patients with variable patterns of hypoxemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.R. 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Semenza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/physrev.00030.2011" "Revista" => array:6 [ "tituloSerie" => "Physiol Rev" "fecha" => "2012" "volumen" => "92" "paginaInicial" => "967" "paginaFinal" => "1003" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22811423" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000005700000008/v1_202108020527/S0300289620305317/v1_202108020527/en/main.assets" "Apartado" => array:4 [ "identificador" => "49741" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Scientific Letters / Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005700000008/v1_202108020527/S0300289620305317/v1_202108020527/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289620305317?idApp=UINPBA00003Z"]

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Scientific Letter

Differences in Overexpression of Hypoxia-induced Transcription Factors and Associated Biomarkers in Three Different Types of Chronic Hypoxia

Diferencias en la sobreexpresión de biomarcadores asociados a la hipoxia en tres tipos de hipoxia diferentes

Maria Isabel Asensio-Cruza,b, Carmen Calero-Acuñaa,b, Elena Arellano-Ordena,b, Verónica Sánchez-Lópeza,b, Candelaria Caballero-Erasoa,b,

Corresponding author

ccaballero-ibis@us.es

Corresponding author.

, Pilar Cejudoa,b, Jose Luis Lopez-Villalobosa, Jose Luis Lopez-Camposa,b, Francisco Ortega-Ruiza,b, Ángeles Sánchez-Armengola

a Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Spain

b Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Research into the impact of hypoxia has focused on chronic continuous hypoxia &#40;CCH&#41;&#44; characteristic of COPD<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> and chronic intermittent hypoxia &#40;CIH&#41;&#44; characteristic of sleep apnea&#8211;hypopnea syndrome &#40;OSA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a> The co-existence of CCH and CIH results in a third type of hypoxia&#44; &#8220;Overlap Syndrome&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The mechanisms of adaptation to these different types of hypoxia may be different&#44; with changes on the cardiovascular system or the peripheral musculature&#44; with a dose-response associated with hypoxia&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We hypothesized that the three models of hypoxia behave differently in the expression of hypoxia-induced transcription factors &#40;factor inducible hypoxia 1&#8211;2 and factor nuclear Kappa-B&#44;NF-KB&#41;&#44; as well as inflammatory biomarkers including tumor necrosis factor &#945; &#40;TNF-&#945;&#41;&#44; interleukin &#40;IL&#41;-8&#44; IL-6&#44; vascular endothelial growth factor &#40;VEGF&#41;&#44; vascular cell adhesion protein 1 &#40;VCAM-1&#41;&#44; and biomarkers of oxidative stress including superoxide dismutase &#40;SOD&#41; and catalase activities &#40;CAT&#41;&#44; both systemically and in the peripheral muscle&#46; Our objective was to compare the mechanisms of adaptation in patients with three types of hypoxia&#44; on the expression of transcription factors sensitive to hypoxia&#44; the expression of systemic inflammation&#44; oxidative stress level and antioxidant capacity&#44; at the systemic and at the muscle levels&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This prospective&#44; observational&#44; cross-sectional study was conducted in male patients over 18 years&#44; diagnosed with COPD&#44; OSA or Overlap Syndrome&#44; further a control group&#46; All subjects underwent a clinical evaluation&#44; spirometry with bronchodilator testing and a home respiratory polygraphy &#40;Embletta Gold PG System&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The COPD patients had FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80&#37; in post-bronchodilator spirometry&#44; a daytime arterial partial pressure of oxygen &#40;PaO<span class="elsevierStyleInf">2</span>&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mmHg and an apnea&#8211;hypopnea index &#40;AHI&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5&#46; The OSA patients had FEV1<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>80&#37;&#44; a PaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>80<span class="elsevierStyleHsp" style=""></span>mmHg&#44; an AHI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15 and had not received CPAP treatment previously&#46; The overlap group had FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80&#37;&#44; a PaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mmHg and an AHI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15&#46; The control group had a normal spirometry with an AHI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Blood samples were collected by venipuncture and were immediately centrifuged&#44; and plasma aliquots were stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Muscle biopsy samples were obtained from all patients &#40;not in control group&#41; from the vast lateral of the quadriceps muscle&#44; frozen in liquid nitrogen and preserved at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; For the analysis in plasma&#44; we selected hypoxia-associated transcription factors&#44; inflammatory&#44; oxidative stress and antioxidants biomarkers&#46; In the muscle biopsies we analyzed the gene expression of the inflammatory markers using reverse transcription quantitative polymerase chain reaction &#40;RT-qPCR&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The study included 34 subjects&#58; 4 with COPD&#44; 12 with OSA&#44; 13 with overlap and 5 controls&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The plasma concentration of transcription factors&#44; inflammation and oxidative stress markers presented significant differences in the three groups of patients compared to the controls &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In plasma&#44; the NF-KB1 was higher and SOD was significantly decreased in the OSA group compared with COPD and Overlap Syndrome&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">As regards the muscle gene expression of transcription factors &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; we found that in COPD patients the expression of VCAM-1 was higher and SOD was lower than in OSA and overlap groups&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In the OSA group we found a significant correlation &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;579&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;04&#41; between the levels of NF-KB1 obtained in plasma and in muscle&#44; besides a significant correlation between the inflammatory and oxidative biomarkers in plasma and in muscle&#58; plasma IL8-muscle SOD &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;69&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#59; plasma endothelin-muscle CAT &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;61&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;03&#41;&#59; plasma ICAM-muscle IL8 &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;71&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;009&#41; and plasma ICAM-muscle CAT &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In COPD group there was an increase in muscle expression of VCAM-1 compared to OSA&#44; and a decreased in SOD compared with the other two groups&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The three groups of hypoxemic patients show an overexpression of hypoxia-sensitive transcription factors&#44; primarily HIF-1&#945;&#44; compared to control subjects&#46; In OSA there was an increase in plasma levels of NF-&#954;B1 compared to COPD group&#46; In situations of CIH&#44; overexpression of NF-&#954;B1 in plasma has been demonstrated in a cell culture model<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> with a selective activation of inflammatory pathways&#44; unlike CCH hypoxia of patients with COPD and overlap&#44; where the activation of adaptive pathways predominates&#46; Oxidative stress driven by CIH may initiate systemic inflammation in OSA&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> which inflammatory response in turn promoting the development of cardiovascular morbidities&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> We have found a decrease in the plasma of SOD in OSA patients&#46; In situations with a chronically oxidative stress due to overexpression of NF-&#954;B1&#44; there may be a decrease in SOD by a saturation of the antioxidant systems&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">We found no differences between the three patient groups in the expression of transcription factors in peripheral musculature&#46; However&#44; in COPD there is a higher level of VCAM and lower SOD than in OSA&#44; reflecting a more intense inflammatory state at the muscle&#44; besides a lower ability to nullify the deleterious effect of free radicals&#46; These findings match with the findings of other authors<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> and agree with that muscle dysfunction in COPD is clinically important&#46; In patients with CCH&#44; inflammatory and oxidative processes in plasma and in muscle fiber seem to be independent&#46; In OSA&#44; there is a correlation between the levels of the NF-KB in plasma and in muscle fiber&#44; as well as between parameters of inflammatory and antioxidant status in plasma and peripheral muscle&#44; suggesting that inflammation and oxidative stress at the systemic levels and in the muscle are interrelated processes&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In summary&#44; the three groups of hypoxemic patients show an overexpression of hypoxia-sensitive transcription factors&#44; with a higher expression of NF-&#954;B in OSA&#46; In plasma&#44; an increase in oxidative stress is evident in the three groups&#44; but the deficit in antioxidant substances is greater in OSA&#44; which may be due to the overexpression of NF-&#954;B&#46; At peripheral muscle&#44; there were no differences in inflammatory parameters&#44; unlike the response to oxidative stress&#44; with an increase in the production of free radicals and a decrease in antioxidant substances in COPD patients versus OSA patients&#46; Inflammation and oxidative stress in plasma and muscle in COPD and COPD-OSA seem to be independent phenomena&#46; In OSA&#44; inflammatory and oxidative stress levels in muscle fiber are related to systemic levels&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding Source</span><p id="par0070" class="elsevierStylePara elsevierViewall">Grants for projects of the Association of Pulmonologists of the South&#46; Neumosur&#46; Project&#58; Expression of transcription factors sensitive to hypoxia&#44; inflammatory response and oxidative stress at the systemic and muscular level in three clinical models of hypoxemia&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Research grants 2012 SEPAR&#46; Code&#58; 051&#124;2012&#46; Expression of transcription factors sensitive to hypoxia&#44; the inflammatory response&#44; oxidative stress and peripheral muscle involvement in three clinical models of hypoxemia&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; COPD&#58; chronic obstructive pulmonary disease&#59; OSA&#58; sleep apnea&#8211;hypopnea syndrome&#59; HIF-1&#945;&#58; hypoxia inducible factor 1&#44; subunit &#945;&#59; HIF-2&#945;&#58; hypoxia inducible factor 2&#44; subunit &#945;&#59; NF-&#954;B1&#58; nuclear factor kappa-B 1&#59; IL- 6&#58; interleukin-6&#59; IL- 8&#58; interleukin-8&#59; TNF-&#945;&#58; tumor necrosis factor alpha&#59; VEGF&#58; vascular endothelial growth factor&#59; VCAM-1&#58; vascular cell adhesion protein 1&#59; CAT&#58; catalase activity&#59; SOD&#58; superoxide dismutase activity&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">TNF-&#945; &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VEGF &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">VCAM-1 &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">SOD &#40;U&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
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            1 => array:3 [
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              "etiqueta" => "&#8224;"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Plasma Concentration of Transcription Factors&#44; Inflammation and Oxidative Stress Markers&#44; and Muscle Gene Expression of Transcription Factors&#44; Inflammation and Oxidative Stress Parameters&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
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Article information

ISSN: 03002896
Original language: English

DOI:10.1016/j.arbres.2020.11.011

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	3	5	8
2024 October	50	21	71
2024 September	44	22	66
2024 August	64	40	104
2024 July	40	21	61
2024 June	53	22	75
2024 May	70	25	95
2024 April	48	18	66
2024 March	41	16	57
2024 February	36	19	55
2024 January	37	19	56
2023 December	33	24	57
2023 November	34	23	57
2023 October	48	22	70
2023 September	40	43	83
2023 August	48	605	653
2023 July	40	22	62
2023 June	31	18	49
2023 May	49	14	63
2023 April	34	16	50
2023 March	32	20	52
2023 February	39	17	56
2023 January	35	23	58
2022 December	55	26	81
2022 November	59	26	85
2022 October	70	24	94
2022 September	48	23	71
2022 August	39	35	74
2022 July	39	43	82
2022 June	38	37	75
2022 May	45	28	73
2022 April	48	37	85
2022 March	59	48	107
2022 February	20	14	34
2022 January	1	0	1
2021 November	1	0	1
2021 October	4	0	4
2021 September	2	2	4
2021 August	29	16	45
2021 June	2	2	4
2021 March	5	1	6
2021 February	1	2	3
2021 January	1	2	3
2020 December	1	4	5

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