Vitamin D deficiency accelerates atherosclerosis development in diabetes

13 August 2009

MedWire News: Vitamin D deficiency contributes to the increase in macrophage-mediated cholesterol deposition observed in patients with diabetes, report researchers in the journal Circulation.

Vitamin D deficiency is associated with an increased risk for cardiovascular disease in people with diabetes.

To investigate a potential mechanism underlying this association, Carlos Bernal-Mizrachi (Washington University School of Medicine, St. Louis, USA) and co-workers investigated the effects of active vitamin D on macrophage cholesterol deposition in patients with and without Type 2 diabetes.

The researchers obtained (peripheral blood monocytes) from 76 obese, hypertensive, diabetic adults with vitamin D deficiency and four control groups comprising obese, diabetic, hypertensive patients with vitamin D sufficiency (n=15), obese, nondiabetic, hypertensive patients with vitamin D deficiency (n=25), and nonobese, nondiabetic, nonhypertensive patients with (n=10) and without (n=10) vitamin D deficiency.

Each patient’s cells were differentiated into macrophages by culturing with 100 ng/ml of macrophage colony-stimulating factor for 7 days in vitamin D-deficient media.

Foam cell formation, cholesteryl ester formation, and cholesterol uptake, binding, and efflux were assessed in macrophages after stimulation with modified low-density lipoprotein (LDL) cholesterol from the same individuals’ monocytes cultured in vitamin D-deficient or vitamin D-supplemented media for 7 days.

Vitamin D-supplementation suppressed foam cell formation by reducing modified LDL cholesterol uptake in the diabetic patients only. Conversely, deletion of the vitamin D receptor in macrophages from these patients accelerated LDL cholesterol induced foam cell formation.

The authors provide evidence that activation of vitamin D receptor signaling by vitamin D supplementation prevents foam cell formation by reducing expression of two scavenger receptors involved in macrophage cholesterol deposition: CD36 and SR-A1. These receptors play an important role in transforming macrophages into foam cells.

“This study reveals a novel mechanistic link between vitamin D deficiency in macrophages and foam cell formation in Type 2 diabetics,” write the authors.

“These results suggest that modulation of vitamin D signaling is a potential therapeutic target to prevent vascular disease progression,” they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Circulation 2009; 120: 687–698