Abstract
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.
Highlights
Reduced β2-glycoprotein 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
The aim of our study was to investigate how reduced β2-glycoprotein I (β2GP I) by Matrix metalloproteinase (MMP)/Tissue inhibitor of matrix metalloproteinase (TIMP) affect the aorta in vivo, and to determine any related mechanisms of action involved
In the reduced β2GP I group the structure of the vessel wall was intact, the endothelium showed no thickening, and there was no significant foam cell formation (Figure 3)
Summary
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. The latest epidemiological data show that the prevalence of diabetes is 11.6%, and pre-diabetes is 50.1%, in people over 18 years old in China [1]. The macrovascular complications of diabetes mainly cause damage to the cardiovascular system. Diabetes is related to a higher risk of.
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