Beclin-1 increases with obstructive sleep apnea severity

International audienceObstructive sleep apnea is a common chronic disorder that leads to chronic intermittent hypoxia described as an important factor contributing to the pathogenesis of OSA-related comorbidities. Besides, recent data suggest that intermittent hypoxia can induce adaptative cardiovascular pathways inducing a relative resistance to ischemic insults. Adaptative pathways induced by hypoxia could implicate autophagic processes and Beclin-1, one of the first mammalian autophagy effectors. Thus, activation of autophagy could protect against cardiovascular events in patients with OSA and could be considered as biomarker of a better prognosis

Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease.

International audienceChronic obstructive pulmonary disease (COPD) is a major risk factor for cardiovascular disease. Polycythemia, a common complication of hypoxic COPD, may affect systemic vascular function by altering blood viscosity, vessel wall shear stress (WSS), and endothelium-derived nitric oxide (NO) release. Here, we evaluated the effects of hypoxia-related polycythemia on systemic endothelial function in patients with COPD. We investigated blood viscosity, WSS, and endothelial function in 15 polycythemic and 13 normocythemic patients with COPD of equal severity, by recording brachial artery diameter variations in response to hyperemia and by using venous occlusion plethysmography (VOP) to measure forearm blood flow (FBF) responses to a brachial artery infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP), substance P (SP), isoptin, and N-monomethyl-l-arginine (l-NMMA). At baseline, polycythemic patients had higher blood viscosity and larger brachial artery diameter than normocythemic patients but similar calculated WSS. Flow-mediated brachial artery vasodilation was increased in the polycythemic patients, in proportion to the hemoglobin levels. ACh-induced vasodilation was markedly impaired in the polycythemic patients and negatively correlated with hemoglobin levels. FBF responses to endothelium- (BK, SP) and non-endothelium-dependent (SNP, isoptin) vasodilators were not significantly different between the two groups. l-NMMA infusion induced a similar vasoconstrictor response in both groups, in accordance with their similar baseline WSS. In conclusion, systemic arteries in polycythemic patients adjust appropriately to chronic or acute WSS elevations by appropriate basal and stimulated NO release. Overall, our results suggest that moderate polycythemia has no adverse effect on vascular function in COPD

Telomere Shortening in Middle-Aged Men with Sleep-disordered Breathing

International audienceRationale: Sleep disorders may lead to stress-induced premature aging and telomere shortening.Objectives: To determine whether obstructive sleep apnea syndrome causing intermittent hypoxemic episodes was associated with telomere shortening independently from the comorbidities associated with this syndrome.Methods: We conducted a cross-sectional study in 161prospectivelly enrolled, untreated, middle-aged men free of known comorbidities related or unrelated to sleep apnea. Each participant underwent full standard overnight polysomnography. Patients with apnea sleep syndrome were naive to treatment.Measurements and main results: In univariate analysis, we found that telomere shortening was associated with older age, apnea-hypopnea index, oxygen desaturation index, waist circumference, and fat mass. After adjustment for age, only apnea-hypopnea index and oxygen desaturation index were significantly related to telomere shortening. The mean telomere length ratio was 0.70 ± 0.37 in the participants without sleep apnea, compared with 0.61 ± 0.22 and 0.53 ± 0.16 in those with mild to moderate and severe sleep apnea, respectively (P = 0.01). In multivariate analysis, we found that oxygen desaturation index was the only factor independently associated with telomere length. Arterial stiffness assessed by carotid-femoral pulse wave velocity correlated negatively with telomere length.Conclusions: Intermittent hypoxemia due to obstructive sleep apnea syndrome is a major contributor to telomere shortening in middle-aged men. Oxidative stress may explain this finding

Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

<div><p>Rationale</p><p>Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.</p><p>Objectives</p><p>To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DL_CO) corrected for alveolar volume (K_CO).</p><p>Methods</p><p>Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD).</p><p>Measurements and Main Results</p><p>Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low K_CO had lower ASMMI values compared to those with normal K_CO. Moreover, female smokers with low K_CO, had lower BMD and shorter TL compared to those with normal K_CO.</p><p>Conclusions</p><p>Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a K_CO decrease. Decreased K_CO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.</p></div

Characteristics of the study patients.

<p><i>Definition of abbreviations</i>: COPD, chronic obstructive pulmonary disease; % predicted, percentage of the predicted value; BMI, body mass index; MAP, mean arterial pressure; K_CO, transfer factor coefficient of the lung for carbon monoxide; SpO₂, oxygen saturation by pulse oximetry.</p><p>Data are median [interquartile range] unless stated otherwise.</p><p>†<i>P</i> value by Chi-square test, Fisher exact test, or nonparametric Kruskal-Wallis test, as appropriate, comparing the three populations (COPD patients, control smokers, and nonsmokers).</p><p>Characteristics of the study patients.</p

Comparison of inflammatory mediators between smokers with low K_CO and those with normal K_CO.

<p>K_CO, transfer factor coefficient of the lung for carbon monoxide; IL, interleukin; MCP-1, monocyte chemotactic protein-1; TNF-α, tumor necrosis factor alpha</p><p>Data are median [interquartile range].</p><p>† <i>P</i> value by nonparametric Kruskal-Wallis test</p><p>Comparison of inflammatory mediators between smokers with low K_CO and those with normal K_CO.</p