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Chest Jan 2017Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to... (Review)
Review
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in pulmonary artery smooth muscle cells (PASMC). This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and hypoxia-inducible factor (HIF)-1α, leading to adverse pulmonary vascular remodeling and pulmonary hypertension (PH). In the nonventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis, which optimizes systemic Po without altering pulmonary artery pressure (PAP). In single-lung anesthesia, HPV reduces blood flow to the nonventilated lung, thereby facilitating thoracic surgery. At altitude, global hypoxia causes diffuse HPV, increases PAP, and initiates PH. Exaggerated or heterogeneous HPV contributes to high-altitude pulmonary edema. Conversely, impaired HPV, whether due to disease (eg, COPD, sepsis) or vasodilator drugs, promotes systemic hypoxemia. Genetic and epigenetic abnormalities of this oxygen-sensing pathway can trigger normoxic activation of HIF-1α and can promote abnormal metabolism and cell proliferation. The resulting pseudohypoxic state underlies the Warburg metabolic shift and contributes to the neoplasia-like phenotype of PH. HPV and oxygen sensing are important in human health and disease.
Topics: Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Oxygen Consumption; Pulmonary Circulation; Pulmonary Gas Exchange; Vasoconstriction
PubMed: 27645688
DOI: 10.1016/j.chest.2016.09.001 -
Respiratory Care Jun 2019For more than 40 years, noninvasive ventilation has been the first-line preferred therapy for acute-on-chronic conditions, such as COPD and cardiogenic pulmonary edema.... (Review)
Review
For more than 40 years, noninvasive ventilation has been the first-line preferred therapy for acute-on-chronic conditions, such as COPD and cardiogenic pulmonary edema. The use of noninvasive ventilation in the treatment of hypoxemic respiratory failure, however, has been met with mixed results associated with higher risks of intubation (failure of therapy) and with higher risks of mortality. The purpose of this review was to describe the current evidence and important considerations when patients with hypoxemic respiratory failure are managed with noninvasive ventilation.
Topics: Acute Disease; Humans; Hypoxia; Noninvasive Ventilation; Patient Selection; Practice Guidelines as Topic; Respiratory Insufficiency; Risk Factors; Severity of Illness Index
PubMed: 31110033
DOI: 10.4187/respcare.06735 -
Respiratory Care Oct 2014Oxygen is essential for normal aerobic metabolism in mammals. Hypoxia is the presence of lower than normal oxygen content and pressure in the cell. Causes of hypoxia... (Review)
Review
Oxygen is essential for normal aerobic metabolism in mammals. Hypoxia is the presence of lower than normal oxygen content and pressure in the cell. Causes of hypoxia include hypoxemia (low blood oxygen content and pressure), impaired oxygen delivery, and impaired cellular oxygen uptake/utilization. Many compensatory mechanisms exist at the global, regional, and cellular levels to allow cells to function in a hypoxic environment. Clinical management of tissue hypoxia usually focuses on global hypoxemia and oxygen delivery. As we move into the future, the clinical focus needs to change to assessing and managing mission-critical regional hypoxia to avoid unnecessary and potential toxic global strategies. We also need to focus on understanding and better harnessing the body's own adaptive mechanisms to hypoxia.
Topics: Adaptation, Physiological; Humans; Hypoxia; Oxygen; Oxygen Inhalation Therapy
PubMed: 25161296
DOI: 10.4187/respcare.03357 -
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 -
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 -
Nature Reviews. Immunology Dec 2017Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological... (Review)
Review
Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.
Topics: Animals; Cellular Microenvironment; Gene Expression Regulation; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Immune System; Immunity; Immunity, Innate; Immunomodulation; Inflammation; Signal Transduction; Transcription, Genetic
PubMed: 28972206
DOI: 10.1038/nri.2017.103 -
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 -
American Journal of Physiology.... Nov 2014Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in... (Review)
Review
Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigation, including potentially the severity of hypoxia within episodes, the duration of hypoxic episodes, the number of hypoxic episodes per day, the pattern of presentation across time (e.g., within vs. consecutive vs. alternating days), and the cumulative time of exposure. Not surprisingly, severe/chronic IH protocols tend to be pathogenic, whereas any beneficial effects are more likely to arise from modest/acute IH exposures. Features of the IH protocol most highly associated with beneficial vs. pathogenic outcomes include the level of hypoxemia within episodes and the number of episodes per day. Modest hypoxia (9-16% inspired O2) and low cycle numbers (3-15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2-8% inspired O2) and more episodes per day (48-2,400 episodes/day) elicit progressively greater pathology. Accumulating evidence suggests that "low dose" IH (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders.
Topics: Animals; Bone and Bones; Cardiovascular System; Humans; Hypoxia; Inflammation; Nervous System; Oxygen; Respiratory System; Time Factors
PubMed: 25231353
DOI: 10.1152/ajpregu.00208.2014 -
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