title: The Protective Effect of Interleukin-37 on Vascular Calcification and Atherosclerosis in Apolipoprotein E-Deficient Mice with Diabetes.
abstract: 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.
authors: 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 .
authors: Meng
authors: M
authors: Chai
authors: 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 .
authors: Qingwei
authors: Q
authors: Ji
authors: 3 Department of Cardiology, General Hospital of the Air Force , Beijing, China .
authors: Haitao
authors: H
authors: Zhang
authors: 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 .
authors: Yujie
authors: Y
authors: Zhou
authors: 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 .
authors: Qing
authors: Q
authors: Yang
authors: 4 School of General Medicine and Continuing Education, Capital Medical University , Beijing, China .
authors: Yangwei
authors: Y
authors: Zhou
authors: 3 Department of Cardiology, General Hospital of the Air Force , Beijing, China .
authors: Guangjin
authors: G
authors: Guo
authors: 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 .
authors: Wei
authors: W
authors: Liu
authors: 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 .
authors: Wei
authors: W
authors: Han
authors: 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 .
authors: Lixia
authors: L
authors: Yang
authors: 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 .
authors: Linlin
authors: L
authors: Zhang
authors: 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 .
authors: Jing
authors: J
authors: Liang
authors: 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 .
authors: Yuyang
authors: Y
authors: Liu
authors: 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 .
authors: Dongmei
authors: D
authors: Shi
authors: 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 .
authors: Yingxin
authors: Y
authors: Zhao
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D061205:Vascular Calcification / Q000097:blood / Q000150:complications* / Q000188:drug therapy*
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D002316:Cardiotonic Agents; C508587:IL37 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D053244:Osteoprotegerin; D000469:Alkaline Phosphatase