Atherosclerosis is Lessened by Glycine-Based Therapy that St | 90731
International Research Journals

International Research Journal of Biochemistry and Bioinformatics

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Atherosclerosis is Lessened by Glycine-Based Therapy that Stimulates Glutathione Production


Richie Rich*

Lower circulating glycine levels are frequently linked to cardiovascular disease (CVD); however it is still unknown whether glycine has a causal or therapeutic function in atherosclerosis, the primary factor in most CVDs. Following the discovery that individuals with severe coronary artery disease (sCAD) had lower levels of circulating glycine, we looked into the possibility that glycine plays a causal role in atherosclerosis by altering the availability of glycine in atheroprone mice. We also assessed DT-109's potential for atheroprotection, a newly discovered glycine-based molecule with dual lipid and glucose-lowering characteristics. In apolipoprotein E-deficient (Apoe/) mice, glycine deprivation accelerated atherosclerosis development whereas glycine supplementation slowed it down (Rom O et al., 2016). The most notable atheroprotective benefits were shown with the use of DT-109, which also decreased superoxide levels and atherosclerosis across the whole aortic tree and aortic sinus. With no lipid-lowering effects, DT-109 therapy dramatically decreased aortic superoxide and atherosclerosis in Apoe/ animals with advanced atherosclerosis. Studies on the kinetics and targeted metabolomics of DT-109 have shown that it causes mononuclear cells to produce glutathione. Glycine and DT-109 reduced the production of superoxide in bone marrow-derived macrophages (BMDMs) in response to glycine deprivation. This was eliminated in glutamate-cysteine ligase modifier subunit-deficient (Gclm/-) animals, which have a problem with glutathione production. Glycine deficit reduces glutathione production in BMDMs, but glycine-based therapy stimulates de novo glutathione biosynthesis, according to metabolic flow and carbon tracing tests. We showed that glycine plays a causal role in atherosclerosis and identified glycine-based therapy as a strategy through investigations in patients with CAD, in vivo studies using atherosclerotic mice, and in vitro studies utilizing macrophages.

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