title: Effects of reduced β2-glycoprotein I on the expression of aortic matrix metalloproteinases and tissue inhibitor matrix metalloproteinases in diabetic mice.
abstract: BACKGROUND
  Reduced β(2)-glycoprotein I (reduced β(2)GP 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 β(2)GP 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 β(2)GP I, reduced β(2)GP 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 β(2)GP I, reduced β(2)GP 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 β(2)GP I group were lower than those in the diabetic group. Aortic lipid deposition in the reduced β(2)GP I group was significantly less than in the diabetic control group. In the aortas, reduced β(2)GP I decreased MMP2/TIMP2 mRNA and protein expression levels, and MMP9/TIMP1 expression levels compared with those in diabetic controls. Reduced β(2)GP 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 β(2)GP 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Penghua
authors.initials: P
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Meijun
authors.initials: M
authors.lastname: Wang
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.affiliation: 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. wbyp1998@hotmail.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Demin
authors.initials: D
authors.lastname: Yu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D001018:Aortic Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D059305:Diet, High-Fat; D019422:Dietary Sucrose; D015536:Down-Regulation; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000737:chemistry / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008078:Cholesterol, LDL; D019422:Dietary Sucrose; D012333:RNA, Messenger; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D053482:beta 2-Glycoprotein I; D019716:Tissue Inhibitor of Metalloproteinase-2; D013311:Streptozocin; D048051:p38 Mitogen-Activated Protein Kinases; D017364:Collagenases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse