| Vitamin D regulates macrophage cholesterol metabolism in diabetes. | |
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MedLine Citation:
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PMID: 20338238 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In type 2 diabetics, the prevalence of vitamin D deficiency is 20% higher than in non-diabetics, and low vitamin D levels nearly double the relative risk of developing CVD compared to diabetic patients with normal vitamin D levels. However, the mechanism(s) by which vitamin D deficiency leads to an increased susceptibility to atherosclerosis in these patients is unknown. We studied the effects of vitamin D replacement on macrophage cholesterol metabolism and foam cell formation in obese, hypertensive diabetics and non-diabetic controls. We found that 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] suppressed foam cell formation by reducing acetylated low density lipoprotein (AcLDL) and oxidized low density lipoprotein (oxLDL) cholesterol uptake in diabetics only. 1,25(OH)2D3 downregulation of c-Jun N-terminal kinase activation reduced PPARgamma and CD36 expression, and prevented oxLDL-derived cholesterol uptake. In addition, 1,25(OH)2D3 suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxLDL- and AcLDL-derived cholesterol uptake. The results of this research reveal novel insights into the mechanisms linking vitamin D signaling to foam cell formation in diabetics and suggest a potential new therapeutic target to reduce cardiovascular risk in this population. |
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Authors:
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Amy E Riek; Jisu Oh; Carlos Bernal-Mizrachi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2010-03-23 |
Journal Detail:
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Title: The Journal of steroid biochemistry and molecular biology Volume: 121 ISSN: 1879-1220 ISO Abbreviation: J. Steroid Biochem. Mol. Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-19 Completed Date: 2010-09-20 Revised Date: 2012-02-03 |
Medline Journal Info:
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Nlm Unique ID: 9015483 Medline TA: J Steroid Biochem Mol Biol Country: England |
Other Details:
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Languages: eng Pagination: 430-3 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 South Euclid Avenue, St. Louis, MO 63110, United States. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / metabolism Cardiovascular Diseases / complications Cholesterol / metabolism* Diabetes Complications / metabolism Diabetes Mellitus / metabolism* Foam Cells / metabolism Gene Expression Regulation* Humans Inflammation Insulin / metabolism Macrophages / metabolism* Risk Vitamin D / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P30 DK056341-10/DK/NIDDK NIH HHS; R01 HL094818-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Insulin; 1406-16-2/Vitamin D; 57-88-5/Cholesterol |
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