ArticleCirculation research2011
Hypoxia is present in murine atherosclerotic plaques and has multiple adverse effects on macrophage lipid metabolism.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Association between non-alcoholic fatty liver disease and obstructive sleep apnea.World journal of gastroenterology · 2020Pooled it
- Causal relationship between nonalcoholic fatty liver disease and different sleep traits: a bidirectional Mendelian randomized study.Frontiers in endocrinology · 2023Trial
- Regulatory networks involved in modulating fat deposition in pigs identified by gene co-expression analysis.BMC genomics · 2026Article
- Hydroxychloroquine Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice: Role of Endothelial Nitric Oxide Synthase and Hypoxia-Inducible Factor 1-Alpha.Cardiology research · 2026Article
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Hypermetabolism and Lipid Alterations Postburn: A Cardiovascular Perspective.Cardiovascular therapeutics · 2026Review
- The role of Western diet and gut microbiota in the pathogenesis of cardiovascular diseases.Frontiers in microbiology · 2026Review
- Obstructive sleep apnea is ralated to metabolic dysfunction associated steatotic liver disease in type 2 diabetes mellitus.Scientific reports · 2025Article
- Metabolism Serves as a Bridge Between Cardiomyocytes and Immune Cells in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2025Review
- Liposome-mediated macrophage reprogramming: emerging strategies for chronic disease therapy.Frontiers in immunology · 2025Review
- The role of CXCL16 in atherosclerosis: from mechanisms to therapy.Frontiers in immunology · 2025Review
- Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection.International journal of drug discovery and pharmacology · 2024Article
- Immunometabolism in atherosclerotic disorders.Nature cardiovascular research · 2024Review
- Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors.Nature ecology & evolution · 2024Article
- Evidence for hypoxia-induced dysregulated cholesterol homeostasis in preeclampsia: Insights into the mechanisms from human placental cells and tissues.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Carbon dioxide regulates cholesterol levels through SREBP2.PLoS biology · 2023Article
- Macrophage polarization and metabolism in atherosclerosis.Cell death & disease · 2023Review
- Review
- Hypofucosylation of Unc5b regulated by Fut8 enhances macrophage emigration and prevents atherosclerosis.Cell & bioscience · 2023Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleHuman atherosclerotic plaques contain large numbers of cells deprived of O(2). In murine atherosclerosis, because the plaques are small, it is controversial whether hypoxia can occur.
objectiveTo examine if murine plaques contain hypoxic cells, and whether hypoxia regulates changes in cellular lipid metabolism and gene expression in macrophages. METHODS AND
resultsAortic plaques from apolipoprotein-E-deficient mice were immunopositive for hypoxia-inducible transcription factor (HIF-1α) and some of its downstream targets. Murine J774 macrophages rendered hypoxic demonstrated significant increases in cellular sterol and triglycerides. The increase in sterol content in hypoxic macrophages correlated with elevated 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase activity and mRNA levels. In addition, when macrophages were incubated with cholesterol complexes, hypoxic cells accumulated 120% more cholesterol, predominately in the free form. Cholesterol-efflux assays showed that hypoxia significantly decreased efflux mediated by ATP-binding cassette subfamily A member 1 (ABCA1), whose sub cellular localization was altered in both J774 and primary macrophages. Furthermore, in vivo expression patterns of selected genes from cells in hypoxic regions of murine plaques were similar to those from J774 and primary macrophages incubated in hypoxia. The hypoxia-induced accumulation of sterol and decreased cholesterol efflux was substantially reversed in vitro by reducing the expression of the hypoxia-inducible transcription factor, HIF-1α.
conclusionHypoxic regions are present in murine plaques. Hypoxic macrophages have increased sterol content due to the induction of sterol synthesis and the suppression of cholesterol efflux, effects that are in part mediated by HIF-1α.
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Registered trials
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