Hypoxia in atherogenesis

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Ferns, Gordon A A ; Heikal, Lamia (2016)

The anoxemia theory proposes that an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerosis. There is now substantial evidence that there are regions within the atherosclerotic plaque in which profound hypoxia exists; this may fundamentally change the function, metabolism, and responses of many of the cell types found within the developing plaque and whether the plaque will evolve into a stable or unstable phenotype. Hypoxia is characterized in molecular terms by the stabilization of hypoxia-inducible factor (HIF) 1a, a subunit of the heterodimeric nuclear transcriptional factor HIF-1 and a master regulator of oxygen homeostasis. The expression of HIF-1 is localized to perivascular tissues, inflammatory macrophages, and smooth muscle cells adjacent to the necrotic core of atherosclerotic lesions and regulates several genes that are important to vascular function including vascular endothelial growth factor, nitric oxide synthase, endothelin-1, and erythropoietin. This review summarizes the effects of hypoxia on the functions of cells involved in atherogenesis and the evidence for its potential importance from experimental models and clinical studies.
  • References (161)
    161 references, page 1 of 17

    1. Xiao W, Jia Z, Zhang Q, Wei C, Wang H, Wu Y. Inflammation and oxidative stress, rather than hypoxia, are predominant factors promoting angiogenesis in the initial phases of atherosclerosis. Mol Med Rep. 2015; 12: 3315-22.

    2. Gainer JL. Hypoxia and atherosclerosis. Re-evaluation of the old hypothesis. Atherosclerosis. 1987; 68: 263-6.

    3. Bjornheden T, Levin M, Evaldsson M, Wiklund O. Evidence of hypoxic areas within the arterial wall in vivo. Arterioscl Thromb Vasc Biol. 1999; 19: 870-6.

    4. Mateo J, Izquierdo-Garcia D, Badimon JJ, Fayad ZA, Fuster V. Noninvasive Assessment of Hypoxia in Rabbit Advanced Atherosclerosis Using F-18-fluoromisonidazole Positron Emission Tomographic Imaging. Circ Cardiovasc Imaging. 2014; 7: 312-20.

    5. Kuschel A, Simon P, Tug S. Functional regulation of HIF-1a under normoxiauis there more than post-translational regulation? J Cell Physiol. 2012; 227: 514-24.

    6. Wu D, Yotnda P. Induction and Testing of Hypoxia in Cell Culture. J Vis Exp. 2011;(54). pii: 2899.

    7. Harris AL. Hypoxia- a key regulatory factor in tumour growth. Nat Rev Cancer. 2002; 2: 38-47.

    8. Giaccia A, Siim BG, Johnson RS. HIF-1 as a target for drug development. Nat Rev Drug Discov. 2003; 2: 803-11.

    9. Carroll VA, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1 alpha-versus HIF-2 alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-1, or loss of von Hippel-Lindau function: Implications for targeting the HIF pathway. Cancer Res. 2006; 66: 6264-70.

    10. Lim CS, Kiriakidis S, Sandison A, Paleolog EM, Davies AH. Hypoxia-inducible factor pathway and diseases of the vascular wall. J Vasc Surg. 2013; 58: 219-30.

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