Deficiency of Glycine N-methyltransferase aggravates atherosclerosis in apolipoprotein E-null mice

Chien Yu Chen, Li Chieh Ching, Yi Jen Liao, Yuan Bin Yu, Chia Yuan Tsou, Song Kun Shyue, Yi Ming Arthur Chen, Tzong Shyuan Lee

研究成果: 雜誌貢獻文章

16 引文 斯高帕斯(Scopus)

摘要

The mechanism underlying the dysregulation of cholesterol metabolism and inflammation in atherogenesis is not understood fully. Glycine N-methyltransferase (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 BI. Furthermore, tumor necrosis factor-α-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.
原文英語
頁(從 - 到)744-752
頁數9
期刊Molecular Medicine
18
發行號5
DOIs
出版狀態已發佈 - 五月 2012
對外發佈Yes

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

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