title: Deficiency of glycine N-methyltransferase aggravates atherosclerosis in apolipoprotein E-null mice.
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.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Ching
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Liao
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Yu
authors.forename: Chia-Yuan
authors.initials: CY
authors.lastname: Tsou
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.forename: Yi-Ming Arthur
authors.initials: YM
authors.lastname: Chen
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D015870:Gene Expression; D050938:Glycine N-Methyltransferase / Q000172:deficiency* / Q000235:genetics; D006949:Hyperlipidemias / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D050938:Glycine N-Methyltransferase