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 PPARγ 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.

Original languageEnglish
Pages (from-to)430-433
Number of pages4
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number1-2
StatePublished - Jul 2010


  • Cardiovascular disease
  • Diabetes
  • Macrophage cholesterol metabolism
  • Vitamin D


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