ReviewAntioxidants & redox signaling2014
Molecular mechanisms of action and therapeutic uses of pharmacological inhibitors of HIF-prolyl 4-hydroxylases for treatment of ischemic diseases.
Review in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Global characterization of Dictyostelium discoideum gene and protein expression changes under hypoxic conditions.BMC genomics · 2025Article
- HIF-1α modulates β-catenin pathway to enhance the survival and angiogenesis of PBMSCs under hypoxia environment.World journal of stem cells · 2025Article
- Article
- Hypoxia-Inducible Factor 1-Alpha (HIF-1α) and Cancer: Mechanisms of Tumor Hypoxia and Therapeutic Targeting.Cureus · 2024Review
- The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.International journal of molecular sciences · 2024Review
- Article
- Targeting immunometabolism as an anti-inflammatory strategy.Cell research · 2020Review
- Protein Hydroxylation by Hypoxia-Inducible Factor (HIF) Hydroxylases: Unique or Ubiquitous?Cells · 2019Review
- Carnosine Supplementation Enhances Post Ischemic Hind Limb Revascularization.Frontiers in physiology · 2019Article
- Circadian-Hypoxia Link and its Potential for Treatment of Cardiovascular Disease.Current pharmaceutical design · 2019Review
- Possible Role of PHD Inhibitors as Hypoxia-Mimicking Agents in the Maintenance of Neural Stem Cells' Self-Renewal Properties.Frontiers in cell and developmental biology · 2018Article
- Loss of PHD3 in myeloid cells dampens the inflammatory response and fibrosis after hind-limb ischemia.Cell death & disease · 2017Article
- Hypoxia-regulated mechanisms in the pathogenesis of obesity and non-alcoholic fatty liver disease.Cellular and molecular life sciences : CMLS · 2016Review
- Ethyl 3,4-dihydroxybenzoate (EDHB): a prolyl hydroxylase inhibitor attenuates acute hypobaric hypoxia mediated vascular leakage in brain.The journal of physiological sciences : JPS · 2016Article
- Genomic insights into ayurvedic and western approaches to personalized medicine.Journal of genetics · 2016Review
- Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.Expert opinion on therapeutic targets · 2016Review
- HIF hydroxylase pathways in cardiovascular physiology and medicine.Circulation research · 2015Review
- Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges.Hypoxia (Auckland, N.Z.) · 2015Review
- Hypoxia-inducible factors link iron homeostasis and erythropoiesis.Gastroenterology · 2014Review
- Signaling hypoxia by hypoxia-inducible factor protein hydroxylases: a historical overview and future perspectives.Hypoxia (Auckland, N.Z.) · 2014Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
significanceIn this review, we have discussed the efficacy and effect of small molecules that act as prolyl hydroxylase domain inhibitors (PHDIs). The use of these compounds causes upregulation of the pro-angiogenic factors and hypoxia inducible factor-1α and -2α (HIF-1α and HIF-2α) to enhance angiogenic, glycolytic, erythropoietic, and anti-apoptotic pathways in the treatment of various ischemic diseases responsible for significant morbidity and mortality in humans. RECENT ADVANCES: Sprouting of new blood vessels from the existing vasculature and surgical intervention, such as coronary bypass and stent insertion, have been shown to be effective in attenuating ischemia. However, the initial reentry of oxygen leads to the formation of reactive oxygen species that cause oxidative stress and result in ischemia/reperfusion (IR) injury. This apparent "oxygen paradox" must be resolved to combat IR injury. During hypoxia, decreased activity of PHDs initiates the accumulation and activation of HIF-1α, wherein the modulation of both PHD and HIF-1α appears as promising therapeutic targets for the pharmacological treatment of ischemic diseases. CRITICAL ISSUES: Research on PHDs and HIFs has shown that these molecules can serve as therapeutic targets for ischemic diseases by modulating glycolysis, erythropoiesis, apoptosis, and angiogenesis. Efforts are underway to identify and synthesize safer small-molecule inhibitors of PHDs that can be administered in vivo as therapy against ischemic diseases. FUTURE DIRECTIONS: This review presents a comprehensive and current account of the existing small-molecule PHDIs and their use in the treatment of ischemic diseases with a focus on the molecular mechanisms of therapeutic action in animal models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.