| Tyrphostin AG490 reduces NAPDH oxidase activity and expression in the aorta of hypercholesterolemic apolipoprotein E-deficient mice. | |
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MedLine Citation:
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PMID: 21457788 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Oxidative stress-induced vascular injury represents a major contributor to the pathoetiology of atherosclerosis. Elevated NADPH oxidase (Nox) activity promotes oxidative injury of the cardiovascular cells. Janus-tyrosine-kinase (Jak) family regulate various aspects of the atherosclerotic process e.g., inflammation, cellular growth, proliferation, and migration. Here, we investigated the potential of Jak2 inhibition to counteract Nox-dependent O(2)(•-) formation in atherogenesis in hypercholesterolemic apolipoprotein E-deficient (ApoE(-/-)) mice. Male ApoE(-/-) mice fed a high-fat, cholesterol-rich diet were treated for 5weeks with either vehicle or tyrphostin AG490 (1mg/kg), a specific Jak2 inhibitor. Lucigenin-enhanced-chemiluminescence assay, real-time PCR and Western blot analysis revealed that Nox-derived O(2)(•-) generation, Nox1, Nox2, and Nox4 mRNA and protein levels were significantly elevated in the aortas of ApoE(-/-) mice fed a high-fat diet compared to ApoE(-/-) mice fed a normal diet. Treatment with tyrphostin AG490 significantly reduced the up-regulated Nox activity, the expression of each Nox subtype, as well as the protein level of CD68, a macrophage-specific marker. Morphometric analysis showed a marked reduction of atherosclerotic lesions in the aorta of AG490-treated animals. These data provide new insights into the regulation of vascular Nox by tyrphostins in the cardiovascular system. Since Jak2 transduces the signals of various cardiovascular risk factors, pharmacological manipulation of this signaling pathway may represent a novel strategy to reduce oxidative stress in atherosclerosis. |
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Authors:
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Ioana M Fenyo; Irina C Florea; Monica Raicu; Adrian Manea |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-29 |
Journal Detail:
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Title: Vascular pharmacology Volume: - ISSN: 1879-3649 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-4-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101130615 Medline TA: Vascul Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010. Published by Elsevier Inc. |
Affiliation:
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Nicolae Simionescu' Institute of Cellular Biology and Pathology, 8, B.P. Hasdeu Street, 050568, Bucharest, Romania. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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