Effects of reduced β2-glycoprotein I on the expression of aortic matrix metalloproteinases and tissue inhibitor matrix metalloproteinases in diabetic mice

BMC Cardiovascular Disorders

Research Article

Jun Xu¹  Pei Yu¹  Demin Yu¹  Tong Wang¹  Penghua Wang¹  Sisi Chen¹  Meijun Wang¹ 

[1] 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, the Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No.66 Tong-An Road, 300070, Tianjin, Heping district, China;

关键词: Reduced βGP I;    Diabetes;    Aorta;    MMP;    TIMP;    p38MAPK;    Signaling pathway;   

DOI  :  10.1186/1471-2261-14-114

 received in 2014-03-29, accepted in 2014-09-05,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundReduced β2-glycoprotein I (reduced β2GP I), which has free sulfhydryl groups, is present in plasma and serum; it can protect vascular endothelial cells from damage due to oxidative stress in vitro. We investigated the effects of reduced β2GP I on the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the aortas of diabetic mice.MethodsWe provided 120 female 8-week-old Balb/c mice with a high sugar, high fat diet. After 8 weeks they were injected with streptozotocin to induce diabetes. We treated mice in the mono dose groups with β2GP I, reduced β2GP I, or phosphate-buffered saline (PBS) on day 1 and fed them for 3 weeks. The mice in the complex dose groups were treated with β2GP I, reduced β2GP I, or PBS on days 1 and 22 and fed for 6 weeks. Control mice were given a standard chow diet. Blood lipids were measured at the end of 3 or 6 weeks, and aortas removed to observe morphological and molecular biological changes.ResultsThe low-density lipoprotein cholesterol levels in mice of the reduced β2GP I group were lower than those in the diabetic group. Aortic lipid deposition in the reduced β2GP I group was significantly less than in the diabetic control group. In the aortas, reduced β2GP I decreased MMP2/TIMP2 mRNA and protein expression levels, and MMP9/TIMP1 expression levels compared with those in diabetic controls. Reduced β2GP I down-regulated p38 mitogen-activated protein kinase (p38MAPK) mRNA expression and phosphorylated p38MAPK protein expression compared with those in diabetic controls of the complex dose group.ConclusionsReduced β2GP I plays a role in diabetic mice related to vascular protection, inhibiting vascular lipid deposition, and plaque formation by reducing MMPs/TIMPs expression through down-regulation of the p38MAPK signaling pathway.

【 授权许可】

Unknown   
© Xu et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.