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学科主题: 临床医学
题名:
The compensatory enrichment of sphingosine-1-phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus
作者: 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
发表日期: 2014-04-21
DOI: 10.1186/1475-2840-13-82
卷: 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
所属项目编号: 2008ZX09312-017 ; 2010CB912504 ; 2011CB503900 ; 81370235 ; 81170101 ; 7122106
项目资助者: National S&amp ; T Major Project of China ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing ; PUHSC-University of Michigan JI
WOS记录号: WOS:000335418400001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52521
Appears in Collections:北京大学第一临床医学院_神经内科_期刊论文

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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

Recommended Citation:
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.
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