Vitamine D en aderverkalking*
In een kleine studie onder 43 mensen met en 25 zonder diabetes typ-2 werd de werking van vitamine D onderzocht op aderverkalking, een ziekte die veel bij diabetespatiënten voorkomt. Bij lage
bloedwaarden vitamine D zo bleek uit de studie kunnen monocyten duidelijk beter plakken aan de slagaderwand en het proces van aderverkalking versterken. De deelnemers in de studie met diabetes bleken wel 2x meer kans te hebben op te lage bloedwaarden (<30 ng/ml) vitamine D. Bij zij met diabetes bleken lage bloedwaarden vitamine D twee keer meer kans te geven op
aderverkalking.
Vitamin D Suppression of Endoplasmic Reticulum Stress Promotes an Antiatherogenic Monocyte/Macrophage Phenotype in Type 2 Diabetic Patients*
1. Amy E. Riek‡,1, 2. Jisu Oh‡, 3. Jennifer E. Sprague§,2, 4. Alexandra
Timpson‡, 5. Lisa de las Fuentes, 6. Leon Bernal-Mizrachi‖, 7. Kenneth B. Schechtman** and
8. Carlos Bernal-Mizrachi‡‡‡,3 + Author Affiliations
1. From the Divisions of ‡Endocrinology, Metabolism, and Lipid Research,
2. §Pediatric Endocrinology and Diabetes,
3. Cardiovascular Diseases, and
4. **Biostatistics and
5. the ‡‡Department of Cell Biology and Physiology, Washington University, St. Louis, Missouri 63110 and
6. the ‖Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia 30322
↵3 To whom correspondence should be addressed: Div. of Endocrinology, Metabolism, and Lipid Research, Dept. of Internal Medicine, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8127, St. Louis, MO 63110. Tel.: 314-362-0947; Fax: 314-362-7641; E-mail: cbernal@dom.wustl.edu.
Capsule
Background: Interactions between environmental conditions and monocyte phenotype are critical for the development of vascular complications in diabetes.
Results: Modulation of ER stress by vitamin D controls monocyte/macrophage phenotype and vascular adhesion.
Conclusion: Vitamin D is a natural ER stress reliever that promotes an anti-inflammatory monocyte/macrophage phenotype.
Significance: Vitamin D is a potential therapy to reduce vascular complications in diabetics.
Abstract
Cardiovascular disease is the leading cause of morbidity/mortality in patients with type 2 diabetes mellitus (T2DM), but there is a lack of knowledge about the mechanism(s) of increased atherosclerosis in these patients. In patients with T2DM, the prevalence of 25-hydroxy vitamin D (25(OH)D) deficiency is almost twice that for nondiabetics and doubles the relative risk of developing cardiovascular disease compared with diabetic patients with normal 25(OH)D. We tested the hypothesis that monocytes from vitamin D-deficient subjects will have a proatherogenic phenotype compared with vitamin D-sufficient subjects in 43 patients with T2DM. Serum 25(OH)D level inversely correlated with monocyte adhesion to endothelial cells even after adjustment for demographic and comorbidity characteristics. Vitamin D-sufficient patients (≥30 ng/ml 25(OH)D) had lower monocyte endoplasmic reticulum (ER) stress, a predominance of M1 over M2 macrophage membrane receptors, and decreased mRNA expression of monocyte adhesion molecules PSGL-1, β1-integrin, and β2-integrin compared with patients with 25(OH)D levels of <30 ng/ml. In vitamin D-deficient macrophages, activation of ER stress increased adhesion and adhesion molecule expression and induced an M2-predominant phenotype. Moreover, adding 1,25(OH)2D3 to vitamin D-deficient macrophages shifted their phenotype toward an M1-predominant phenotype with suppressed adhesion. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients activated ER stress, accelerated adhesion, and increased adhesion molecule expression. The absence of ER stress protein CCAAT enhancer-binding protein homologous protein suppressed monocyte adhesion, adhesion molecule expression, and the M2-predominant phenotype induced by vitamin D deficiency. Thus, vitamin D is a natural ER stress reliever that induced an antiatherogenic monocyte/macrophage phenotype.
(November 2012)
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