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Hypoxia Is Present in Murine Atherosclerotic Plaques and Has Multiple Adverse Effects on Macrophage Lipid Metabolism

Hypoxia Is Present in Murine Atherosclerotic Plaques and Has Multiple Adverse Effects on... Integrative Physiology Hypoxia Is Present in Murine Atherosclerotic Plaques and Has Multiple Adverse Effects on Macrophage Lipid Metabolism Sajesh Parathath,* Stephanie L. Mick,* Jonathan E. Feig, Victor Joaquin, Lisa Grauer, David M. Habiel, Max Gassmann, Lawrence B. Gardner, Edward A. Fisher Rationale: Human atherosclerotic plaques contain large numbers of cells deprived of O . In murine atheroscle- rosis, because the plaques are small, it is controversial whether hypoxia can occur. Objective: To examine if murine plaques contain hypoxic cells, and whether hypoxia regulates changes in cellular lipid metabolism and gene expression in macrophages. Methods and Results: Aortic plaques from apolipoprotein-E–deficient mice were immunopositive for hypoxia- inducible transcription factor (HIF-1) 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Circulation Research Wolters Kluwer Health

Hypoxia Is Present in Murine Atherosclerotic Plaques and Has Multiple Adverse Effects on Macrophage Lipid Metabolism

Fisher, Edward A.
Circulation Research , Volume 109 (10) – Oct 1, 2011
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References (65)

Copyright
© 2011 American Heart Association, Inc.
ISSN
0009-7330
eISSN
1524-4571
DOI
10.1161/CIRCRESAHA.111.246363
pmid
21921268
Publisher site
See Article on Publisher Site

Abstract

Integrative Physiology Hypoxia Is Present in Murine Atherosclerotic Plaques and Has Multiple Adverse Effects on Macrophage Lipid Metabolism Sajesh Parathath,* Stephanie L. Mick,* Jonathan E. Feig, Victor Joaquin, Lisa Grauer, David M. Habiel, Max Gassmann, Lawrence B. Gardner, Edward A. Fisher Rationale: Human atherosclerotic plaques contain large numbers of cells deprived of O . In murine atheroscle- rosis, because the plaques are small, it is controversial whether hypoxia can occur. Objective: To examine if murine plaques contain hypoxic cells, and whether hypoxia regulates changes in cellular lipid metabolism and gene expression in macrophages. Methods and Results: Aortic plaques from apolipoprotein-E–deficient mice were immunopositive for hypoxia- inducible transcription factor (HIF-1) 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

Journal

Circulation Research – Wolters Kluwer Health

Published: Oct 1, 2011

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