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Archives of Cardiovascular Diseases May 2020Obstructive sleep apnoea syndrome is a growing health concern, affecting nearly one billion people worldwide; it is an independent cardiovascular risk factor, associated... (Review)
Review
Obstructive sleep apnoea syndrome is a growing health concern, affecting nearly one billion people worldwide; it is an independent cardiovascular risk factor, associated with incident obesity, insulin resistance, hypertension, arrhythmias, stroke, coronary artery disease and heart failure. Obstructive sleep apnoea-related cardiovascular and metabolic co-morbidities are a major concern for prognosis and the complexity of obstructive sleep apnoea integrated care. Continuous positive airway pressure, the first-line therapy for the treatment of obstructive sleep apnoea, is highly effective at improving symptoms and quality of life, but has limited effect on co-morbidities. Deciphering the molecular pathways involved in obstructive sleep apnoea metabolic and cardiovascular consequences is a priority to make new pharmacological targets available, in combination with or as an alternative to continuous positive airway pressure. Intermittent hypoxia, a landmark feature of obstructive sleep apnoea, is the key intermediary mechanism underlying metabolic and cardiovascular complications. Experimental settings allowing intermittent hypoxia exposure in cells, rodents and healthy humans have been established to dissect the molecular mechanisms of obstructive sleep apnoea-related co-morbidities. The main objective of this review is to recapitulate the molecular pathways, cells and tissue interactions contributing to the cardiometabolic consequences of intermittent hypoxia. Sympathetic activation, low-grade inflammation, oxidative stress and endoplasmic reticulum stress are triggered by intermittent hypoxia and play a role in cardiometabolic dysfunction. The key role of hypoxia-inducible factor-1 transcription factor will be detailed, as well as the underestimated and less described importance of mitochondrial functional changes in the intermittent hypoxia setting.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Cell Hypoxia; Endoplasmic Reticulum Stress; Hemodynamics; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Oxidative Stress; Risk Factors; Signal Transduction; Sleep Apnea, Obstructive; Vascular Remodeling
PubMed: 32224049
DOI: 10.1016/j.acvd.2020.01.003 -
Journal of Hematology & Oncology Jun 2022Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells,... (Review)
Review
Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.
Topics: Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunologic Surveillance; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 35659268
DOI: 10.1186/s13045-022-01292-6 -
Respiratory Care Jul 2021Hypoxemia is common in postoperative patients and is associated with prolonged hospital stays, high costs, and increased mortality. This review discusses the... (Review)
Review
Hypoxemia is common in postoperative patients and is associated with prolonged hospital stays, high costs, and increased mortality. This review discusses the postoperative management of hypoxemia in regard to the use of conventional oxygen therapy, high-flow nasal cannula oxygen therapy, CPAP, and noninvasive ventilation. The recommendations made are based on the currently available evidence.
Topics: Cannula; Continuous Positive Airway Pressure; Humans; Hypoxia; Noninvasive Ventilation; Oxygen; Oxygen Inhalation Therapy
PubMed: 34006596
DOI: 10.4187/respcare.08929 -
International Journal of Molecular... Oct 2022Intermittent hypoxia (IH), one of the primary pathologies of sleep apnea syndrome (SAS), exposes cells throughout the body to repeated cycles of hypoxia/normoxia that... (Review)
Review
Intermittent hypoxia (IH), one of the primary pathologies of sleep apnea syndrome (SAS), exposes cells throughout the body to repeated cycles of hypoxia/normoxia that result in oxidative stress and systemic inflammation. Since SAS is epidemiologically strongly correlated with type 2 diabetes/insulin resistance, obesity, hypertension, and dyslipidemia included in metabolic syndrome, the effects of IH on gene expression in the corresponding cells of each organ have been studied intensively to clarify the molecular mechanism of the association between SAS and metabolic syndrome. Dementia has recently been recognized as a serious health problem due to its increasing incidence, and a large body of evidence has shown its strong correlation with SAS and metabolic disorders. In this narrative review, we first outline the effects of IH on the expression of genes related to metabolism in neuronal cells, pancreatic β cells, hepatocytes, adipocytes, myocytes, and renal cells (mainly based on the results of our experiments). Next, we discuss the literature regarding the mechanisms by which metabolic disorders and IH develop dementia to understand how IH directly and indirectly leads to the development of dementia.
Topics: Humans; Diabetes Mellitus, Type 2; Metabolic Syndrome; Hypoxia; Cognition; Dementia
PubMed: 36361741
DOI: 10.3390/ijms232112957 -
Experimental & Molecular Medicine Jun 2019Since the discovery of hypoxia-inducible factor (HIF), numerous studies on the hypoxia signaling pathway have been performed. The role of HIF stabilization during... (Review)
Review
Since the discovery of hypoxia-inducible factor (HIF), numerous studies on the hypoxia signaling pathway have been performed. The role of HIF stabilization during hypoxia has been extended from the induction of a single gene erythropoietin to the upregulation of a couple of hundred downstream targets, which demonstrates the complexity and importance of the HIF signaling pathway. Accordingly, HIF and its downstream targets are emerging as novel therapeutic options to treat various organ injuries. In this review, we discuss the current understanding of HIF signaling in four different organ systems, including the heart, lung, liver, and kidney. We also discuss the divergent roles of HIF in acute and chronic disease conditions and their revealed functions. Finally, we introduce some of the efforts that are being performed to translate our current knowledge in hypoxia signaling to clinical medicine.
Topics: Animals; Heart Diseases; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Kidney Diseases; Liver Diseases; Lung Diseases; Signal Transduction
PubMed: 31221962
DOI: 10.1038/s12276-019-0235-1 -
The New England Journal of Medicine Dec 2020
Topics: Adult; Black or African American; Female; Humans; Hypoxia; Male; Organ Dysfunction Scores; Oximetry; Oxygen; Racism; White People
PubMed: 33326721
DOI: 10.1056/NEJMc2029240 -
Kardiologia Polska Jun 2019High altitude is a fascinating model of hypoxia effects on the human body but is also an extreme environment which directly influences millions of people who either... (Review)
Review
High altitude is a fascinating model of hypoxia effects on the human body but is also an extreme environment which directly influences millions of people who either travel to high altitude locations or live there permanently. A significant progress was made over the past decades in the understanding of physiological background of responses to altitude, and recently a number of studies regarding clinical aspects of high altitude exposure were published. In particular, more is known about the changes occurring in systemic blood pressure in individuals exposed to high altitude as well as on the effects of antihypertensive drugs in this setting. The present article provides an overview of principal physiological and clinical aspects related to systemic blood pressure control and its changes at high altitude, mainly during the acute exposure. The evidence on blood pressure changes at rest and during exercise is discussed, as well as the underlying mechanisms and possible clinical implications.
Topics: Altitude; Altitude Sickness; Antihypertensive Agents; Atmospheric Pressure; Blood Pressure; Humans; Hypertension; Hypoxia
PubMed: 31099758
DOI: 10.33963/KP.14832 -
Redox Biology Jan 2021Keloids exhibit metabolic reprogramming including enhanced glycolysis and attenuated oxidative phosphorylation. Hypoxia induces a series of protective responses in...
Keloids exhibit metabolic reprogramming including enhanced glycolysis and attenuated oxidative phosphorylation. Hypoxia induces a series of protective responses in mammalian cells. However, the metabolic phenotype of keloid fibroblasts under hypoxic conditions remains to be elucidated. The present study aimed to investigate glycolytic activity, mitochondrial function and morphology, and the HIF1α and PI3K/AKT signaling pathways in keloid fibroblasts (KFB) under hypoxic conditions. Our results showed that hypoxia promoted proliferation, migration invasion and collagen synthesis and inhibited apoptosis in KFB. The mRNA levels, protein expressions and enzyme activities of glycolytic enzymes in KFB were higher than those in normal skin fibroblasts (NFB) under normoxia. Moreover, hypoxia remarkedly upregulated glycolysis in KFB. Decreased activities of mitochondrial complexes and abnormal mitochondria were detected in KFB under normoxic conditions and the damage was aggravated by hypoxia. An intracellular metabolic profile assay suggested hypoxia increased glycolytic parameters except glycolytic reserve but inhibited the key parameters of mitochondrial function apart from H leak. Protein levels of HIF1α and phosphorylation levels of the PI3K/AKT signaling pathway were upregulated in the context of 3% oxygen. Enhanced total reactive oxygen species (ROS), mitochondrial ROS (mitoROS) and antioxidant activities of KFB were observed in response to hypoxia. Additionally, autophagy was induced by hypoxia. Our data collectively demonstrated potentiated glycolysis and attenuated mitochondrial function under hypoxia, indicating that altered glucose metabolism regulated by hypoxia could be a therapeutic target for keloids.
Topics: Animals; Cell Hypoxia; Fibroblasts; Glucose; Glycolysis; Hypoxia; Keloid; Phosphatidylinositol 3-Kinases
PubMed: 33278780
DOI: 10.1016/j.redox.2020.101815 -
Journal of Applied Physiology... May 2021The word "hypoxia" has recently come to the attention of the general public on two occasions, the Nobel Prize in Medicine or Physiology in 2019 and the recent COVID-19...
The word "hypoxia" has recently come to the attention of the general public on two occasions, the Nobel Prize in Medicine or Physiology in 2019 and the recent COVID-19 pandemic. In the academic environment, hypoxia is a current topic of research in biology, physiology, and medicine: in October 2020, there were more than 150,000 occurrences of "hypoxia" in the PubMed database. However, the first occurrence is dated to 1945, while the interest for the effects of oxygen lack on the living organisms started in the mid-19th century, when scientists explored high altitude regions and mainly used the terms "anoxia" or "anoxemia." I therefore researched online through multiple databases to look for the first appearance of "hypoxia" and related terms "hypoxemia" and "hypoxybiosis" in scientific literature published in English, German, French, Italian, and Spanish. Viault and Jolyet used "Hypohématose" in 1894, but this term has not been used since. Hypoxybiosis first appeared in 1909 in Germany, then hypoxemia in 1923 in Austria, and hypoxia in 1938 in Holland. It was then exported to the United States where it appeared in 1940 in cardiology and anesthesiology. The clinical distinction between anoxia and hypoxia was clearly defined by Carl Wiggers in 1941. Hypoxia (decrease in oxygen), by essence variable in time and in localization in the body, in contrast with anoxia (absence of oxygen), illustrates the concept of homeodynamics that defines a living organism as a complex system in permanent instability, exposed to environmental and internal perturbations.
Topics: COVID-19; Germany; History, 20th Century; Humans; Hypoxia; Inventions; Netherlands; Pandemics; SARS-CoV-2
PubMed: 33703942
DOI: 10.1152/japplphysiol.00936.2020 -
Frontiers in Endocrinology 2022Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a...
Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as , spp., spp., spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.
Topics: Adipose Tissue; Animals; Gastrointestinal Microbiome; Hypoxia; Liver; Metabolome; Mice; RNA, Ribosomal, 16S; Sleep Deprivation
PubMed: 35178032
DOI: 10.3389/fendo.2022.820939