Abstract 5199: Oral Administration of an Active Form Vitamin D3 Decreases Atherosclerosis in Mice via Modulating Immune Cell Phenotypes and Functions
Background and Objectives: Recent several clinical studies demonstrated the low level of plasma vitamin D3 would be a risk of cardiovascular events. An active form vitamin D3 not only regulates bone metabolisms but also has an immunosuppressive and anti-inflammatory actions which target dendritic cells (DCs) and T lymphocytes. Vitamin D3 has been reported to inhibit the maturation of DCs and to induce regulatory T cells (Tregs) in experimental autoimmune disease models. We hypothesized an active form vitamin D3 (calcitriol), could prevent atherosclerosis through changing immune responses.
Method and Results: Six-week-apolipoprotein E knockout mice on a standard diet were orally administered 200 ng calcitriol dissolved in carboxymethyl cellulose (n=12) or carboxymethyl cellulose alone (n=15; control) twice a week for 12 weeks and atherosclerosis was assessed at 18 weeks old. Calcitriol administration decreased atherosclerotic lesion 39.1 % at aortic sinus compared to control group (mean plaque area: 0.18±0.05×106 vs. 0.27±0.07×106 μm2, p<0.01) without lowering cholesterol. The drug was also shown to reduce the infiltration of inflammatory cells to the atherosclerotic lesions by immunohistochemistry. To evaluate the induction of Tregs and immature state of DCs (iDC) in small intestine and other organs, we examined the ratio of Tregs and iDC by flow cytometry in mesenteric lymph nodes (MLNs) and spleens. Calcitriol markedly increased CD4+CD25+FoxP3+Tregs in MLNs by 17.1% and spleens by 23.4% (p<0.01), and further reduced the mature state (CD11c+CD80+CD86+) DCs in MLNs by 10.6% (p=0.02) compared to control. RT-PCR demonstrated mRNA expressions of CD80 and interferon-gamma were markedly decreased in MLNs and spleens in calcitriol-treated group, respectively.
Conclusion: An active form vitamin D3 could prevent the development of atherosclerosis via changing the function or differentiation of DCs and T lymphocytes. At least, we demonstrated calcitriol increased the number of Tregs and reduced the mature state DCs in the present study, though further studies are required to examine the role of iDC and Tregs in this process. This treatment could be a potential immunotherapy for preventing atherosclerosis and must contribute to the clinics.