Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obstructive sleep apnoea syndrome (OSAS) is characterized by recurrent partial or complete pharyngeal collapses during sleep. The pathophysiology of OSAS is complex and multifactorial. Factors influencing upper airway patency include a reduction in upper airway dimensions that can result from both anatomical and functional alterations (obesity, fluid shift or maxillo-facial structural changes), and increased pharyngeal collapsibility owing to reduced neuromuscular compensation and lack of the pharyngeal protective reflex during sleep. Severe OSAS is associated with a high cardiometabolic risk. Obstructive apnoeic events incorporate a range of stressors that activate mechanisms contributing to the initiation and progression of cardiac, vascular and metabolic diseases. Obstructed breathing induces markedly negative intrathoracic pressure and also provokes hypoxia and hypercapnia. The hypoxaemic stress is further amplified by the subsequent reoxygenation (intermittent hypoxia), resulting in the generation of reactive oxygen species (ROS), sympathetic activation and inflammation. OSAS is able to increase the number of fatal and non-fatal cardiovascular events, including arrhythmias, myocardial infarction and stroke. OSAS is associated with dyslipidemia, type 2 diabetes, its poor control and non-alcoholic fatty liver disease. Screening, diagnosis and integrated care of OSAS should be included in an aggressive management of risk reduction in chronic cardiovascular and metabolic diseases.
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PMID:[Pathophysiology of obstructive sleep apnea syndrome and its cardiometabolic consequences]. 2812 3

Obstructive sleep apnea (OSA), the most severe form of sleep disordered breathing, is characterized by intermittent hypoxia during sleep (IH), sleep fragmentation, and episodic hypercapnia. OSA is associated with increased risk for morbidity and mortality affecting cardiovascular, metabolic, and neurocognitive systems, and more recently with non-alcoholic fatty liver disease (NAFLD) and cancer-related deaths. Substantial variability in OSA outcomes suggests that genetically-determined and environmental and lifestyle factors affect the phenotypic susceptibility to OSA. Furthermore, OSA and obesity often co-exist and manifest activation of shared molecular end-organ injury mechanisms that if properly identified may represent potential therapeutic targets. A challenge in the development of non-invasive diagnostic assays in body fluids is the ability to identify clinically relevant biomarkers. Circulating extracellular vesicles (EVs) include a heterogeneous population of vesicular structures including exosomes, prostasomes, microvesicles (MVs), ectosomes and oncosomes, and are classified based on their size, shape and membrane surface composition. Of these, exosomes (30-100nm) are very small membrane vesicles derived from multi-vesicular bodies or from the plasma membrane and play important roles in mediating cell-cell communication via cargo that includes lipids, proteins, mRNAs, miRNAs and DNA. We have recently identified a unique cluster of exosomal miRNAs in both humans and rodents exposed to intermittent hypoxia as well as in patients with OSA with divergent morbid phenotypes. Here we summarize such recent findings, and will focus on exosomal miRNAs in both adult and children which mediate intercellular communication relevant to OSA and endothelial dysfunction, and their potential value as diagnostic and prognostic biomarkers.
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PMID:Circulating exosomes in obstructive sleep apnea as phenotypic biomarkers and mechanistic messengers of end-organ morbidity. 2867 32