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学科主题: 临床医学
题名:
High-density lipoprotein of patients with Type 2 Diabetes Mellitus upregulates cyclooxgenase-2 expression and prostacyclin I-2 release in endothelial cells: relationship with HDL-associated sphingosine-1-phosphate
作者: Tong, Xunliang1; Peng, Hui5; Liu, Donghui2,3,4; Ji, Liang2,3,4; Niu, Chenguang2,3,4; Ren, Jun6,7; Pan, Bing2,3,4; Hu, Jianying5; Zheng, Lemin2,3,4; Huang, Yining1
关键词: Type 2 diabetes mellitus ; High-density lipoprotein ; Sphingosine-1-phosphate ; Cyclooxygenase-2 ; Prostacyclin I-2 ; Endothelial cells
刊名: CARDIOVASCULAR DIABETOLOGY
发表日期: 2013-01-30
DOI: 10.1186/1475-2840-12-27
卷: 12
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]: SPHINGOSINE 1-PHOSPHATE ; CHOLESTEROL EFFLUX ; MIGRATION ; ATHEROSCLEROSIS ; DYSLIPIDEMIA ; PROTECTION ; RECEPTORS ; GLYCATION ; DISEASE ; RISK
英文摘要:

Background: Dysfunctional high-density lipoprotein (HDL) may have pro-inflammatory effects on the endothelial cells, which causes atherosclerosis in type 2 diabetes mellitus (T2DM). HDL is a major carrier of sphingosine-1-phosphate (S1P) in plasma while S1P exhibits multiple biological activities. However, potential role of HDL and S1P in T2DM remains unexplored. We hypothesized that diabetic HDL with higher contents of S1P exerts beneficial effects on the vascular system.

Methods: Subjects with T2DM with or without proved large arteries atherosclerosis and normal controls (n= 15 for each group) were recruited in the present study. HDL was isolated from the subjects by ultracentrifugation. The levels of HDL-associated S1P were determined by UPLC-MS/MS. The protective function of diabetic HDL and S1P was evaluated by measuring cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release by human umbilical vein endothelial cells (HUVECs) using western blot and enzyme-linked immunosorbent assay (ELISA), respectively.

Results: The S1P levels in isolated HDL were significantly increased in T2DM subjects compared with controls (235.6 +/- 13.4 vs 195.0 +/- 6.4 ng/mg, P< 0.05). The diabetic HDL exerted greater protective effects on inducing COX-2 expression and PGI-2 release by HUVECs than those of control HDL (p < 0.05, p < 0.01, respectively). Pertussis toxin, a common inhibitor of G-couple protein receptors, and VPC 23019, an antagonist of S1P receptor 1 and 3 significantly attenuated HDL-induced COX-2 expression and PGI-2 release.

Conclusions: Diabetic HDL carries higher level of S1P compared with normal HDL, which has the potential to contribute to protective effects on endothelial cells by inducing COX-2 expression and PGI-2 release. These findings provide a new insight of S1P function in T2DM patients, possibly leading to a new therapeutic target.

语种: 英语
所属项目编号: 2008ZX09312-017 ; 2010CB912504 ; 2011CB503900 ; 30900595 ; 81170101 ; 30821001 ; 7102104 ; 7122106
项目资助者: National S&amp ; T Major Project of China ; "973" National ST Major Project ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing, China
WOS记录号: WOS:000316278600001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65277
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, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Sch Basic Med Sci, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci,Minist Educ,Minist Hlt, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 100191, Peoples R China
5.Peking Univ, Coll Urban & Environm Sci, Beijing 100871, Peoples R China
6.Univ Wyoming, Coll Hlth Sci, Div Kinesiol & Hlth, Laramie, WY 82071 USA
7.Univ Wyoming, Coll Hlth Sci, Biomed Sci PhD Program, Laramie, WY 82071 USA

Recommended Citation:
Tong, Xunliang,Peng, Hui,Liu, Donghui,et al. High-density lipoprotein of patients with Type 2 Diabetes Mellitus upregulates cyclooxgenase-2 expression and prostacyclin I-2 release in endothelial cells: relationship with HDL-associated sphingosine-1-phosphate[J]. CARDIOVASCULAR DIABETOLOGY,2013,12.
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