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

BMC Cardiovascular Disorders

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

[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, Heping district, Tianjin, 300070, China

关键词: Signaling pathway;    p38MAPK;    TIMP;    MMP;    Aorta;    Diabetes;    Reduced β₂GP I;   

Others  :  1088458
DOI  :  10.1186/1471-2261-14-114

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

【 摘 要 】

Background

Reduced 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.

Methods

We 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.

Results

The 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.

Conclusions

Reduced 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】

   
2014 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

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