| Selective macrophage ascorbate deficiency suppresses early atherosclerosis. | |
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MedLine Citation:
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PMID: 20974251 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To test whether severe ascorbic acid deficiency in macrophages affects progression of early atherosclerosis, we used fetal liver cell transplantation to generate atherosclerosis-prone apolipoprotein E-deficient (apoE(-/-)) mice that selectively lacked the ascorbate transporter (SVCT2) in hematopoietic cells, including macrophages. After 13 weeks of chow diet, apoE(-/-) mice lacking the SVCT2 in macrophages had surprisingly less aortic atherosclerosis, decreased lesion macrophage numbers, and increased macrophage apoptosis compared to control-transplanted mice. Serum lipid levels were similar in both groups. Peritoneal macrophages lacking the SVCT2 had undetectable ascorbate; increased susceptibility to H(2)O(2)-induced mitochondrial dysfunction and apoptosis; decreased expression of genes for COX-2, IL1β, and IL6; and decreased lipopolysaccharide-stimulated NF-κB and antiapoptotic gene expression. These changes were associated with decreased expression of both the receptor for advanced glycation end products and HIF-1α, either or both of which could have been the proximal cause of decreased macrophage activation and apoptosis in ascorbate-deficient macrophages. |
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Authors:
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Vladimir R Babaev; Richard R Whitesell; Liying Li; MacRae F Linton; Sergio Fazio; James M May |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-23 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 50 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: 2011-05-09 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 27-36 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins E / genetics Ascorbic Acid / adverse effects, metabolism Ascorbic Acid Deficiency / genetics*, metabolism, pathology Atherosclerosis / etiology, genetics*, pathology, prevention & control* Cells, Cultured Disease Progression Female Genetic Predisposition to Disease / prevention & control Macrophages, Peritoneal / metabolism*, pathology, physiology Male Mice Mice, Inbred C57BL Mice, Knockout Organ Specificity / genetics Organic Anion Transporters, Sodium-Dependent / genetics*, metabolism, physiology Sodium-Coupled Vitamin C Transporters Symporters / genetics*, metabolism, physiology Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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DK020593/DK/NIDDK NIH HHS; DK050435/DK/NIDDK NIH HHS; DK59637/DK/NIDDK NIH HHS; GM15431/GM/NIGMS NIH HHS; HL057986/HL/NHLBI NIH HHS; HL065405/HL/NHLBI NIH HHS; HL065709/HL/NHLBI NIH HHS; HL086988/HL/NHLBI NIH HHS; R01 DK050435-15/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Organic Anion Transporters, Sodium-Dependent; 0/Slc23a2 protein, mouse; 0/Sodium-Coupled Vitamin C Transporters; 0/Symporters; 50-81-7/Ascorbic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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