The Protective Effect of Interleukin-37 on Vascular Calcification and Atherosclerosis in Apolipoprotein E-Deficient Mice with Diabetes
The Protective Effect of Interleukin-37 on Vascular Calcification and Atherosclerosis in Apolipoprotein E-Deficient Mice with Diabetes
复制标题
白细胞介素37对载脂蛋白E缺陷型糖尿病小鼠血管钙化和动脉粥样硬化的保护作用
DOI：
10.1089/jir.2014.0212
复制
发表时间：
2015-07-01
影响因子：
2.3
通讯作者：
Zhao, Yingxin
中科院分区：
文献类型：
--
作者：
Chai, Meng;Ji, Qingwei;Zhao, Yingxin
白细胞介素 (IL)-37 是细胞因子 IL-1 家族中新发现的成员。最近的证据表明，IL-37（一种抗炎因子）可能在动脉粥样硬化中发挥作用。在这项研究中，我们使用apoE缺陷的糖尿病小鼠（一种已建立的动物模型）来检查IL-37对血管钙化和动脉粥样硬化进展的影响。与对照组相比，IL-37处理（注射重组蛋白16周）的动物通过von Kossa和茜素红染色检测到的钙化面积显着减少，主动脉根部苏木精-伊红染色检测到的动脉粥样硬化病变斑块尺寸更小，斑块易损性评分更低。我们的数据还表明，IL-37 治疗导致血清中骨保护素 (OPG) 浓度升高。我们检测到接受额外抗 OPG 抗体的组降低了 IL-37 治疗的效果。同时接受IL-37和抗OPG的组比IL-37治疗组具有显着更大的钙化病变面积百分比和动脉粥样硬化斑块尺寸。疾病相关细胞因子（例如 ALP、BMP-2、TNF-α、IL-18 和 IL-10）也发生显着变化。这是首次报道 IL-37 不仅可以减轻动脉粥样硬化，还可以减轻血管钙化。这项研究可能为预防和治疗钙化和动脉粥样硬化疾病提供治疗潜力。
Interleukin (IL)-37 is a newly discovered member of the cytokine IL-1 family. Recent evidence suggests that IL-37, an anti-inflammatory factor, may have a role in atherosclerosis. In this study we used apoE-deficient diabetic mice, an established animal model, to examine the effects of IL-37 on the progression of vascular calcification and atherosclerosis. Compared with the control groups, IL-37-treated (with injection of recombinant protein for 16 weeks) animals had significantly less calcification areas detected by both von Kossa and Alizarin Red staining, and much smaller plaque size of the atherosclerotic lesions and lower plaque vulnerability scores detected by hematoxylin-eosin staining in the aorta root. Our data also showed that IL-37 treatment caused elevated concentrations of osteoprotegerin (OPG) in serum. We detected that the group that received additional anti-OPG antibody reduced the effect of IL-37 treatment. The group that received both IL-37 and anti-OPG had significant larger percentage area of calcified lesion and atherosclerotic plaque size than the IL-37-treated group. Significant changes in disease-relevant cytokines (eg, ALP, BMP-2, TNF-alpha, IL-18, and IL-10) were also elicited. This is the first report that IL-37 could attenuate not only atherosclerosis, but also vascular calcification. This study may offer a therapeutic potential for the prevention and treatment of calcification and atherosclerotic disease.