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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)744-752
Number of pages9
JournalMolecular Medicine
Volume18
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Fingerprint

Glycine N-Methyltransferase
Apolipoproteins E
Atherosclerosis
Macrophages
Cholesterol
Inflammation
Scavenger Receptors
Foam Cells
ATP-Binding Cassette Transporters
Hypermethioninemia
Hyperlipidemias
Lipid Metabolism
LDL Cholesterol
Aorta
Liver Diseases
Down-Regulation
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

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

Cite this

Deficiency of Glycine N-methyltransferase aggravates atherosclerosis in apolipoprotein E-null mice. / Chen, Chien Yu; Ching, Li Chieh; Liao, Yi Jen; Yu, Yuan Bin; Tsou, Chia Yuan; Shyue, Song Kun; Chen, Yi Ming Arthur; Lee, Tzong Shyuan.

In: Molecular Medicine, Vol. 18, No. 5, 05.2012, p. 744-752.

Research output: Contribution to journalArticle

Chen, Chien Yu ; Ching, Li Chieh ; Liao, Yi Jen ; Yu, Yuan Bin ; Tsou, Chia Yuan ; Shyue, Song Kun ; Chen, Yi Ming Arthur ; Lee, Tzong Shyuan. / Deficiency of Glycine N-methyltransferase aggravates atherosclerosis in apolipoprotein E-null mice. In: Molecular Medicine. 2012 ; Vol. 18, No. 5. pp. 744-752.
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