title: Hypoxia in Atherogenesis.
abstract: 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) 1α, 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.
authors: 1 Department of Medical Education, Brighton & Sussex Medical School, Brighton, United Kingdom.
authors: Gordon A A
authors: GAA
authors: Ferns
authors: 1 Department of Medical Education, Brighton & Sussex Medical School, Brighton, United Kingdom.
authors: Lamia
authors: L
authors: Heikal
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011379:Prognosis
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen
keywords: EPO; HIF-1; animal models; hypoxia; sleep apnea; vasa vasorum