JBC：维生素D或可抑制糖尿病患者动脉的阻塞

2012年11月20日 --糖尿病病人常常会发生动脉阻塞，引发心脏病，近日来自华盛顿大学医学院的研究者揭示了低水平的维生素D是导致糖尿病病人产生动脉阻塞的元凶，相关研究刊登于11月9日的国际杂志Journal of Biological Chemistry上，文章揭示，足量维生素D水平的糖尿病患者很少会发生动脉的堵塞。

这项研究中，研究者对43名患有II型糖尿病的患者以及25名无糖尿病的参与者（两组人群年龄、性别、体重等均相似）进行了研究，测定了其维生素D的水平。结果显示，在低水平维生素D（<30毫微克/毫升血液）的糖尿病患者中，其巨噬细胞更多地吸附于血管壁上，容易诱发细胞装载胆固醇，最终诱发血管变得僵硬以及血流量减慢。

研究者Riek说，我们考虑了所有的因素，包括血压、胆固醇、糖尿病控制以及体重等因素，如今我们用小鼠进行实验，看是否维生素D可以抑制巨噬细胞吸附于血管壁上，同时我们也进行了两组病人的临床试验。

研究者给糖尿病和高血压病人以维生素D，观察是否这种疗法可以降低其血压，另一项研究中，研究者评估了是否维生素D的补充可以减缓或者逆转患者心脏病的发生。研究者希望知道是否维生素D的疗法可以逆转和心血管疾病发生相关的风险因子。

未来研究中，研究者希望开发出以维生素D为基础的疗法来抑制血管中胆固醇的累积，乃至心血管疾病的发生。相关研究由国家心肺与血液研究所等机构提供资助。

与糖尿病相关的拓展阅读：

• JAMA：研究支持对糖尿病患者进行更强力的抗血小板治疗
• Obes Surg：减重手术可能不能“治愈”糖尿病
• Cell Metab:新的血清标志物提前数年预测糖尿病风险
• Circulation：精氨酸酶抑制剂治疗糖尿病患者并发症
• Diabetologia：维生素D缺乏与1型糖尿病 更多信息请点击：有关糖尿病更多资讯

Vitamin D Suppression of Endoplasmic Reticulum Stress Promotes an Antiatherogenic Monocyte/Macrophage Phenotype in Type 2 Diabetic Patients*

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.

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