Chai Meng, Ji Qingwei, Zhang Haitao, Zhou Yujie, Yang Qing, Zhou Yangwei, Guo Guangjin, Liu Wei, Han Wei, Yang Lixia, Zhang Linlin, Liang Jing, Liu Yuyang, Shi Dongmei, Zhao Yingxin
1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University , Beijing, China .
2 The Key Laboratory of Remodeling-Related Cardiovascular Disease, Beijing Institute of Heart , Lung and Blood Vessel Disease, Ministry of Education, Beijing, China .
J Interferon Cytokine Res. 2015 Jul;35(7):530-9. doi: 10.1089/jir.2014.0212. Epub 2015 Apr 13.
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-α, 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.
白细胞介素（IL）-37是细胞因子IL-1家族新发现的成员。最近的证据表明，抗炎因子IL-37可能在动脉粥样硬化中发挥作用。在本研究中，我们使用载脂蛋白E缺陷型糖尿病小鼠（一种成熟的动物模型）来研究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，经IL-37处理（注射重组蛋白16周）的动物，经冯科萨染色和茜素红染色检测到的钙化面积显著减少，苏木精-伊红染色检测到的主动脉根部动脉粥样硬化病变的斑块大小明显更小，斑块易损性评分更低。我们的数据还表明，IL-37处理导致血清中骨保护素（OPG）浓度升高。我们检测到，额外接受抗OPG抗体的组降低了IL-37处理的效果。同时接受IL-37和抗OPG的组的钙化病变面积百分比和动脉粥样硬化斑块大小显著大于经IL-37处理的组。还引发了与疾病相关的细胞因子（如碱性磷酸酶、骨形态发生蛋白-2、肿瘤坏死因子-α、白细胞介素-18和白细胞介素-10）的显著变化。这是第一份关于IL-37不仅可以减轻动脉粥样硬化，还可以减轻血管钙化的报告。本研究可能为钙化和动脉粥样硬化疾病的预防和治疗提供治疗潜力。
