Journal
MOLECULAR MEDICINE
Volume 18, Issue 5, Pages 744-752Publisher
SPRINGER
DOI: 10.2119/molmed.2011.00396
Keywords
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Funding
- National Science Council [NSC-99-2320-B-010-017-MY3]
- National Health Research Institutes [NHRI-EX100-9608SC]
- VGHUST Joint Research Program, Tsou's Foundation [VGHUST 100-G7-4-4, VGHUST 101-G7-5-3]
- Yen Tjing Ling Medical Foundation [CI-99-15, CI-100-26]
- Ministry of Education, Aim for the Top University Plan, VGHUST Joint Research Program, Taiwan
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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
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