| Glutathione peroxidase-deficient smooth muscle cells cause paracrine activation of normal smooth muscle cells via cyclophilin A. | |
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MedLine Citation:
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PMID: 21782974 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Reduced activity of the antioxidant glutathione peroxidase-1 (GPx1) correlates with increased risk of cardiovascular events in patients with coronary artery disease. However, it remains unclear whether this imbalance in antioxidant capacity directly contributes to activation of vascular cells. In response to oxidative stress, smooth muscle cells (SMCs) secrete the pro-inflammatory immunomodulator cyclophilin A (CyPA). We hypothesized that reduction in vascular cell GPx1 activity causes secretion of CyPA and paracrine-mediated activation of NF-κB and proliferation of SMCs. METHODS/RESULTS: Using a murine model of GPx1 deficiency (GPx1(+/-)), we found elevated levels of hydrogen peroxide levels and increased secretion of CyPA in both arterial segments and cultured SMCs as compared to wild type (WT). Conditioned media from GPx1(+/-) SMCs caused increased NF-κB activation of quiescent WT SMCs, and this was inhibited by the antioxidant N-acetyl-l-cysteine or by cyclosporine A (CsA). In co-culture experiments, SMCs derived from GPx1(+/-) aorta caused increased proliferation of WT SMCs, which was also inhibited by CsA. CONCLUSIONS: Reduction in vascular cell GPx1 activity and the associated increase in oxidative stress cause CyPA-mediated paracrine activation of SMCs. These findings identify a novel mechanism by which an imbalance in antioxidant capacity may contribute to vascular disease. |
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Authors:
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Maysam Takapoo; Ali H Chamseddine; Ramesh C Bhalla; Francis J Miller |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-12 |
Journal Detail:
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Title: Vascular pharmacology Volume: - ISSN: 1879-3649 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 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 © 2011. Published by Elsevier Inc. |
Affiliation:
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Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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