期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 121, 期 1-2, 页码 430-433出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2010.03.018
关键词
Vitamin D; Diabetes; Cardiovascular disease; Macrophage cholesterol metabolism
资金
- NHLBI NIH HHS [R01 HL094818] Funding Source: Medline
- NIDDK NIH HHS [P30 DK056341-10] Funding Source: Medline
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 D-3 [1,25(OH)(2)D-3] 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)(2)D-3 down-regulation of c-Jun N-terminal kinase activation reduced PPAR gamma and CD36 expression, and prevented oxLDL-derived cholesterol uptake. In addition, 1,25(OH)(2)D-3 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. (C) 2010 Elsevier Ltd. All rights reserved.
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