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Deficiency of glycine N-methyltransferase aggravates atherosclerosis in apolipoprotein E-null mice.
- Source :
-
Molecular medicine (Cambridge, Mass.) [Mol Med] 2012 Jul 18; Vol. 18, pp. 744-52. Date of Electronic Publication: 2012 Jul 18. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Apolipoproteins E genetics
Biological Transport
Cholesterol metabolism
Gene Expression
Glycine N-Methyltransferase genetics
Hyperlipidemias genetics
Inflammation genetics
Lipid Metabolism drug effects
Lipoproteins, LDL pharmacology
Macrophages drug effects
Macrophages immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Tumor Necrosis Factor-alpha pharmacology
Apolipoproteins E deficiency
Atherosclerosis genetics
Glycine N-Methyltransferase deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1528-3658
- Volume :
- 18
- Database :
- MEDLINE
- Journal :
- Molecular medicine (Cambridge, Mass.)
- Publication Type :
- Academic Journal
- Accession number :
- 22415010
- Full Text :
- https://doi.org/10.2119/molmed.2011.00396