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The compensatory enrichment of sphingosine-1-phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus
Tong, Xunliang1; Lv, Pu1; Mathew, Anna V.5; Liu, Donghui6; Niu, Chenguang2,3,4; Wang, Yan6; Ji, Liang2,3,4; Li, Jizhao2,3,4; Fu, Zhiwei2,3,4; Pan, Bing2,3,4; Pennathur, Subramaniam5; Zheng, Lemin2,3,4; Huang, Yining1
关键词Sphingosine 1 Phosphate High Density Lipoprotein Type 2 Diabetes Mellitus Cyclooxygenase-2 Endothelial Cells
刊名CARDIOVASCULAR DIABETOLOGY
2014-04-21
DOI10.1186/1475-2840-13-82
13
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Endocrinology & Metabolism
研究领域[WOS]Cardiovascular System & Cardiology ; Endocrinology & Metabolism
关键词[WOS]APOLIPOPROTEIN-A-I ; NONENZYMATIC GLYCATION ; HDL ; ATHEROSCLEROSIS ; METABOLISM ; MYELOPEROXIDASE ; CYCLOOXYGENASE ; DYSLIPIDEMIA ; CHOLESTEROL ; IMPAIRMENT
英文摘要

Background: Glycation of high-density lipoprotein (HDL) decreases its ability to induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in endothelial cells. Whether lipid content of HDL, especially sphingosine-1-phosphate (S1P), plays any specific role in restoring the protective function of HDL in type 2 diabetes mellitus (T2DM) is still unknown.

Methods and results: Immunochemical techniques demonstrated that glycated HDL loses its protective function of regulating COX-2 expression compared with diabetic HDL. We proved that the lipid content, especially phospholipid content differed between diabetic HDL and glycated HDL. Levels of HDL-c-bound S1P were increased in T2DM compared with control subjects as detected by UPLC-MS/MS (HDL-c-bound S1P in control subjects vs. T2DM: 309.1 +/- 13.71 pmol/mg vs. 382.1 +/- 24.45 pmol/mg, P < 0.05). Additionally, mRNA levels of S1P lyase enzymes and S1P phosphatase 1/2 were decreased in peripheral blood by real-time PCR. Antagonist of S1P receptor 1 and 3 (S1PR1/3) diminished the functional difference between apoHDL&PL (HDL containing the protein components and phospholipids) and diabetic apoHDL&PL (diabetic HDL containing the protein components and phospholipids). With different doses of S1P reconstituted on glycated HDL, its function in inducing the COX-2 expression was restored to the same level as diabetic HDL. The mechanism of S1P reconstituted HDL (rHDL) in the process of regulating COX-2 expression involved the phosphorylation of ERK/MAPK-CREB signal pathway.

Conclusion/Significance: S1P harbored on HDL is the main factor which restores its protective function in endothelial cells in T2DM. S1P and its receptors are potential therapeutic targets in ameliorating the vascular dysfunction in T2DM.

语种英语
WOS记录号WOS:000335418400001
项目编号2008ZX09312-017 ; 2010CB912504 ; 2011CB503900 ; 81370235 ; 81170101 ; 7122106
资助机构National S&amp ; T Major Project of China ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing ; PUHSC-University of Michigan JI
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52521
专题北京大学基础医学院
北京大学第一临床医学院_神经内科
作者单位1.Peking Univ, Hosp 1, Dept Neurol, Beijing 100034, Peoples R China
2.Peking Univ, Inst Cardiovasc Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Inst Syst Biomed, Hlth Sci Ctr, Beijing 100191, Peoples R China
4.Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ,Minist Hlth,Hlth Sci Ctr, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 100191, Peoples R China
5.Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
6.Xiamen Univ, Xiamen Heart Ctr, Zhongshan Hosp, Div Cardiol, Xiamen 361004, Fujian Province, Peoples R China
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GB/T 7714
Tong, Xunliang,Lv, Pu,Mathew, Anna V.,et al. The compensatory enrichment of sphingosine-1-phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus[J]. CARDIOVASCULAR DIABETOLOGY,2014,13.
APA Tong, Xunliang.,Lv, Pu.,Mathew, Anna V..,Liu, Donghui.,Niu, Chenguang.,...&Huang, Yining.(2014).The compensatory enrichment of sphingosine-1-phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus.CARDIOVASCULAR DIABETOLOGY,13.
MLA Tong, Xunliang,et al."The compensatory enrichment of sphingosine-1-phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus".CARDIOVASCULAR DIABETOLOGY 13(2014).
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