Deficiency of Glycine N-Methyltransferase Aggravates Atherosclerosis in Apolipoprotein E-Null Mice

被引：19

作者：

Chen, Chien-Yu ^{[1
]}

Ching, Li-Chieh ^{[1
]}

Liao, Yi-Jen ^{[2
]}

Yu, Yuan-Bin ^{[3
]}

Tsou, Chia-Yuan ^{[1
]}

Shyue, Song-Kun ^{[5
]}

Chen, Yi-Ming Arthur ^{[2
]}

Lee, Tzong-Shyuan ^{[1
,4
]}

机构：

[1] Natl Yang Ming Univ, Dept Physiol, Sch Med, Taipei 11221, Taiwan

[2] Natl Yang Ming Univ, Dept Microbiol, Sch Med, Taipei 11211, Taiwan

[3] Taipei Vet Gen Hosp, Div Hematol & Oncol, Taipei, Taiwan

[4] Natl Yang Ming Univ, Brain Res Ctr, Taipei 112, Taiwan

[5] Acad Sinica, Inst Biomed Sci, Div Cardiovasc, Taipei, Taiwan

来源：

MOLECULAR MEDICINE | 2012年 / 18卷 / 05期

关键词：

CASSETTE TRANSPORTER A1; FOLATE-BINDING-PROTEIN; MACROPHAGE FOAM CELL; HEPATOCELLULAR-CARCINOMA; S-ADENOSYLMETHIONINE; TANGIER-DISEASE; GENE; EXPRESSION; ABCA1; SUSCEPTIBILITY;

D O I：

10.2119/molmed.2011.00396

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The mechanism underlying the dysregulation of cholesterol metabolism and inflammation in atherogenesis is not understood fully. Glycine N-methyltransfercise (GNMT) has been implicated in hepatic lipid metabolism and the pathogenesis of liver diseases. However, little is known about the significance of GNMT in atherosclerosis. We showed the predominant expression of GNMT in foamy macrophages of mouse atherosclerotic aortas. Genetic deletion of GNMT exacerbated the hyperlipidemia, inflammation and development of atherosclerosis in apolipoprotein E-deficient mice. In addition, ablation of GNMT in macrophages aggravated oxidized low-density lipoprotein-mediated cholesterol accumulation in macrophage foam cells by downregulating the expression of reverse cholesterol transporters including ATP-binding cassette transporters-A1 and G1 and scavenger receptor B1. Furthermore, tumor necrosis factor-alpha-induced inflammatory response was promoted in GNMT-null macrophages. Collectively, our data suggest that GNMT is a crucial regulator in cholesterol metabolism and in inflammation, and contributes to the pathogenesis of atherosclerosis. This finding may reveal a potential therapeutic target for atherosclerosis. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00396

引用

页码：744 / 752

页数：9

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