{"id":25898,"date":"2024-06-25T04:12:00","date_gmt":"2024-06-24T20:12:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=25898"},"modified":"2024-06-25T05:55:03","modified_gmt":"2024-06-24T21:55:03","slug":"icu-management-practice-%e6%8f%ad%e7%a4%bahif-1%ce%b1%e5%9c%a8%e8%84%93%e6%af%92%e7%97%87%e4%b8%ad%e7%9a%84%e4%bd%9c%e7%94%a8","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=25898","title":{"rendered":"[ICU Management &#038; Practice]: \u63ed\u793aHIF-1\u03b1\u5728\u8113\u6bd2\u75c7\u4e2d\u7684\u4f5c\u7528"},"content":{"rendered":"\n<h1 class=\"wp-block-heading\">Unravelling the Role of HIF-1\u03b1 in Sepsis<\/h1>\n\n\n\n<ul>\n<li>In&nbsp;<a href=\"https:\/\/healthmanagement.org\/c\/sepsis\">Sepsis<\/a><\/li>\n\n\n\n<li>Tue, 2 Apr 2024<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/res.cloudinary.com\/healthmanagement-org\/image\/upload\/c_thumb,f_auto,fl_lossy,h_700,q_80,w_1000\/v1712064914\/cw\/00126726_cw_image_wi_9160bb026c457810782b7c7a4bca7724.jpg\" alt=\"\"\/><\/figure>\n\n\n\n<p>A recent review explores the crucial role of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) in the development and progression of sepsis.&nbsp;<\/p>\n\n\n\n<p><br \/>Hypoxia-inducible factor (HIF) is a protein complex consisting of a constitutively expressed subunit \u03b2 and an oxygen-dependent subunit \u03b1. HIF-1\u03b1 is associated with acute hypoxia and regulates glycolytic genes, oxygen consumption, and reactive oxygen species production. It belongs to the bHLH-PAS family, facilitating dimer formation with HIF-1\u03b2 and binding to hypoxia response elements (HRE) on target genes. HIF-1\u03b1 contains transactivation domains (TAD) that stabilise the protein and prevent degradation.<\/p>\n\n\n\n<p>HIF-2\u03b1 functions predominantly in chronic hypoxia, regulating erythropoietin synthesis, iron metabolism, fatty acid synthesis and uptake, and influencing chronic inflammation, fibrosis, and tumorigenesis. HIF-3\u03b1 also plays a role in the hypoxia response, competitively binding to transcriptional elements of target genes during hypoxia and negatively regulating gene expression associated with the HIF pathway.<\/p>\n\n\n\n<p>In bacterial sepsis, elevated levels of HIF-1\u03b1 are observed, stimulated by the immune response to various bacterial pathogens such as Streptococcus pyogenes, Staphylococcus aureus, and Pseudomonas aeruginosa. Tissue inflammation induces local hypoxia due to increased oxygen consumption from bacterial infection and the migration\/proliferation of immune cells at the infection site. Bacterial components like outer membrane proteins or LPS from Escherichia coli upregulate HIF-1\u03b1 levels. Additionally, cytokines released post-infection, such as interleukins (IL-6, IL-4, IL-12, IL-1) and tumour necrosis factor-alpha (TNF-\u03b1), also contribute to increased HIF-1\u03b1 expression.<\/p>\n\n\n\n<p>In viral sepsis, elevated levels of HIF-1\u03b1 are observed in response to viral infections. Certain viruses can accumulate HIF-1\u03b1 by inhibiting prolyl hydroxylase (PHD) degradation pathways. Activated inflammatory pathways during the immune response can also induce higher HIF-1\u03b1 levels. Pattern recognition receptors (PRRs) activate innate immunity, triggering inflammatory responses and HIF-1\u03b1 production. Finally, some respiratory viruses can directly damage lung tissue, causing hypoxia and further elevating HIF-1\u03b1 levels.<\/p>\n\n\n\n<p>Hypoxia plays a crucial role in shaping the host microenvironment during fungal infections. Infection foci or biofilms formed by host cells and fungi lead to localised hypoxia, worsened by vascular damage reducing oxygen delivery. This oxygen scarcity triggers a hypoxic response in fungi, increasing levels of HIF-1\u03b1. HIF-1\u03b1 assumes a protective role in fungal infections, reducing Candida albicans colonisation in the gastrointestinal tract. Additionally, upregulation of HIF-1\u03b1 alleviates airway inflammation in mouse models exposed to Aspergillus fumigatus.<\/p>\n\n\n\n<p>Sepsis triggers an immune response through the recognition of microbial products and endogenous danger signals by the complement system and cell-surface receptors, leading to inflammatory dysregulation. Pathogen-associated molecular patterns (PAMPs) from invading microorganisms initiate immune responses, releasing inflammatory factors and activating the innate immune system. Additionally, injuries like sepsis, trauma, and burns release endogenous pattern recognition receptor agonists called damage-associated molecular patterns (DAMPs), further inducing inflammation. These interlocking positive feedback loops between PAMPs, DAMPs, and their receptors underlie the systemic inflammatory response to infection or tissue damage. Inflammatory factors modulate HIF-1\u03b1 levels, influencing various physiological and pathological processes.&nbsp;<\/p>\n\n\n\n<p>Recent clinical studies have aimed to translate HIF-1\u03b1 research findings into clinical applications, particularly in post-diagnostic and prognostic aspects of sepsis. Prospective studies have shown significantly elevated levels of HIF-1\u03b1 mRNA in the blood of shock patients compared to healthy volunteers, indicating its potential diagnostic relevance. Similarly, serum HIF-1\u03b1 levels in intensive care patients have demonstrated diagnostic potential in sepsis, with significantly higher concentrations detected in patients with septic shock and septic non-shock compared to those undergoing elective surgery. Combining HIF-1\u03b1 with other clinical parameters has shown high diagnostic accuracy for sepsis, revealing a U-shaped relationship between HIF-1\u03b1 levels and ICU mortality.<\/p>\n\n\n\n<p>HIF-1\u03b1 plays a critical role in sepsis, activated not only by intracellular hypoxia but also by the inflammatory process and immune regulation. Its activation governs the host's adaptive response to hypoxia during sepsis and influences the release of inflammatory mediators and the balance between anti-inflammatory and immune tolerance states. Additionally, HIF-1\u03b1 activation regulates various pathophysiological processes such as mitochondrial function and apoptosis. Future studies can delve into the molecular mechanisms and pathways of HIF-1\u03b1 in sepsis, potentially revealing new targets and strategies for the early diagnosis and treatment of this condition.<\/p>\n\n\n\n<p><br \/>Source:&nbsp;<a href=\"https:\/\/ccforum.biomedcentral.com\/articles\/10.1186\/s13054-024-04885-4\" target=\"_blank\" rel=\"noreferrer noopener\">Critical Care<\/a><br \/>Image Credit: iStock&nbsp;<\/p>\n\n\n\n<p><a href=\"https:\/\/healthmanagement.org\/c\/cybersecurity\/news\/impact-and-aftermath-of-the-change-healthcare-cyberattack-insights-from-the-aha\">\u00ab\u00ab&nbsp;Impact and Aftermath of the Change Healthcare Cyberattack: Insights from the AHA<\/a><\/p>\n\n\n\n<p><a href=\"https:\/\/healthmanagement.org\/c\/cardio\/news\/efficacy-and-safety-of-tirzepatide\">Efficacy and Safety of Tirzepatide \u00bb\u00bb<\/a><\/p>\n\n\n\n<h4 class=\"wp-block-heading\">References:<\/h4>\n\n\n\n<p>Ruan H, Zhang Q, Zhang Yp et al. (2024)&nbsp;<a href=\"https:\/\/ccforum.biomedcentral.com\/articles\/10.1186\/s13054-024-04885-4\" target=\"_blank\" rel=\"noreferrer noopener\">Unraveling the role of HIF-1\u03b1 in sepsis: from pathophysiology to potential therapeutics\u2014a narrative review<\/a>. Crit Care. 28, 100.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Unravelling the Role of HIF-1\u03b1 in Sepsis A recent revie [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/25898"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=25898"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/25898\/revisions"}],"predecessor-version":[{"id":25899,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/25898\/revisions\/25899"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=25898"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=25898"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=25898"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}