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The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes

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Abstract

It was found that glucose in the range of concentrations 12.5–100 mM stimulated Cu2+–mediated free radical peroxidation of low-density lipoproteins (LDL) from human blood plasma. Considering the kinetic parameters of LDL peroxidation we proposed that intensification of this process may be caused by formation of free radical intermediates of glucose auto-oxidation. Addition of SOD to the medium inhibited LDL oxidation, indicating the formation of superoxide anion-radicals under autoxidation of glucose. Similarly, SOD inhibited free radical peroxidation of liposomes from egg lecithin in the presence of glucose that confirms the generation of superoxide radicals under co-oxidation of unsaturated lipids and glucose. Normalization of glucose level in the blood of patients with type 2 diabetes mellitus during therapy was accompanied by a significant decrease in LDL oxidation in vivo (the decrease in primary and secondary lipoperoxidation products). The formation of superoxide anion-radicals was observed during interaction of aminoacid l-lysine with a product of glucose oxidative metabolism–methylglyoxal, but not with a product of lipoperoxidation malonyldialdehyde. In accordance with the foregoing the administration of sugar-lowering drug metformin, which binds and utilizes methylglyoxal, caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals. Based on the results we set out the hypothesis about autocatalytic mechanism of free radical reactions involving natural dicarbonyls and suppose the common molecular mechanism of vascular wall injury in atherosclerosis and diabetes.

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Acknowledgments

This work was supported by the grant of Russian scientific foundation No.14-15-00245. The authors are very grateful to MD Ludmila Nedosuga for the organization and conduct of clinical studies of patients with diabetes at the Department of Endocrinology, Sechenov’s Moscow Medical Academy and for the provision of clinical material for biochemical analyzes.

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Authors and Affiliations

  1. Russian Cardiology Research Complex, 3-rd Cherepkovskaya 15A, Moscow, 121552, Russia

    Vadim Lankin, Galina Konovalova, Alla Tikhaze, Konstantin Shumaev & Elena Kumskova

  2. Tallinn Technology University, Ehitajate tee 5, 19086, Tallinn, Estonia

    Margus Viigimaa

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  1. Vadim Lankin
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  2. Galina Konovalova
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Correspondence to Vadim Lankin.

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Lankin, V., Konovalova, G., Tikhaze, A. et al. The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes. Mol Cell Biochem 395, 241–252 (2014). https://doi.org/10.1007/s11010-014-2131-2

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