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Cited by 318Cancer, Hypoxia, and MetabolismErythropoietin and Anemia TreatmentHigh Altitude and Hypoxia

Pathophysiological implications of hypoxia in human diseases

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Chen, Pai-Sheng, Chiu, Wen-Tai, Hsu, Pei-Ling, Lin, Shih-Chieh, Peng, I-Chen, Wang, Chia-Yih, Tsai, Shaw-Jenq·2020·Journal of Biomedical Science
DOI 10.1186/s12929-020-00658-7PMC PMC7212687
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Abstract

Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.

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  • Aberrant regulation of hypoxic signaling is mechanistically associated with disease development across ischemic heart disease, stroke, cancer, and chronic obstructive pulmonary disease.

    “Aberrant regulation of hypoxic signaling is mechanistically associated with disease development across a range of conditions, including ischemic heart disease, stroke, cancer, and chronic obstructive pulmonary disease [15]”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [15]

    The Abstract (no page given) links hypoxia to the pathogenesis of cancer and myocardial ischemia, and the ‘Hypoxia and human diseases’ section describes mechanisms in cancer and cardiovascular injury. That section mentions stroke as a risk of atherosclerosis and identifies chronic obstructive pulmonary disease as a hypoxic pulmonary disease, but it does not establish that dysregulated hypoxic signaling contributes mechanistically to the development of either condition. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Dysregulation of HIF signaling contributes to disease-associated dysfunction in cancer, ischemic disease, and chronic inflammatory disorders.

    “its dysregulation contributes to disease-associated dysfunction in cancer, ischemic disease, and chronic inflammatory disorders”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [15]

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Cited by

Sorted by citations

Authors
Chen, P.-S., Chiu, W.-T., Hsu, P.-L., Lin, S.-C., Peng, I.-C., Wang, C.-Y., & Tsai, S.-J.
Affiliations
National Cheng Kung University (TW)
Corresponding author
Tsai, Shaw-Jenq
ORCID
Venue
Journal of Biomedical Science
Publisher
Springer Science and Business Media LLC
Published
2020-05-11
Volume
27
Issue
1
Pages
63-63
ISSN
  • 1021-7770 (ISSN-L)
  • 1423-0127
DOI
10.1186/s12929-020-00658-7
PMC
PMC7212687
OpenAlex
W3023575085
Cited by
318
References
28
Citations by year
2026: 29 · 2025: 82 · 2024: 55 · 2023: 64 · 2022: 52 · 2021: 25 · 2020: 7 · 2019: 4
FWCI
3.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biomedical Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Health Research Institutes (NHRI-EX106-10516BI)
  • Ministry of Science and Technology, Taiwan (MOST 106-2320-B-006 -072 -MY3, MOST 107-2321-B-006-014)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
Keywords
hypoxia, chronic hypoxia, intermittent hypoxia, oxygen sensing, hypoxia adaptation, cancer, myocardial ischemia, metabolic disorders, chronic kidney disease, preeclampsia, endometriosis
MeSH terms
Hypoxia, Chronic Disease, Endometriosis, Female, Heart Diseases, Humans, Kidney Diseases, Male, Metabolic Diseases, Neoplasms, Pre-Eclampsia, Pregnancy, Myocardial Ischemia

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