Role of Oxidative Stress in the Genesis of Atherosclerosis and Diabetes Mellitus: A Personal Look Back on 50 Years of Research.
We have provided an overview, based on the literature and our data. In accordance with the theory of D. Harman free radical processes cause damages that can accumulate and contribute to aging of the organism. Atherosclerosis and diabetes are developing for a long time so they are manifested predominantly in old age. We found an increase in the level of free radical peroxidation products and decrease in the activity of antioxidant enzymes in the tissues of animals with experimental atherosclerosis. Similar changes were found in the blood of patients with atherosclerosis and aortic autopsy material with atherosclerotic lesions. Thus, it was revealed that oxidative stress occured under atherosclerosis, and the arteriosclerosis to &quot;Free Radical Pathologies&quot; was attributed. Later it was discovered by different authors that oxidized Low Density Lipoproteins (LDL) and malonyldialdehyde- modified LDL accumulated during atherogenesis, causing damages of vascular wall. Under diabetic hyperglycemia glucose co-oxidized during free radical lipoperoxidation. This process promoted the transformation of oxidative stress to carbonyl stress with accumulation of biologically active dicarbonyls, including glyoxal and methylglyoxal. We show that the glyoxal-modified LDL were captured by cultured macrophages with a higher efficiency than the MDA-modified LDL. This could facilitate the more rapid development of lipoidosis in the vessel wall (due to the formation of foam cells) and manifestation of atherosclerosis under diabetes. We found that in patients with diabetes there was a sharp decrease in the activity of antioxidant enzymes as a result of the modification of the active center under development of carbonyl stress. We expressed a hypothesis about a common molecular mechanism of vascular wall damages under atherosclerosis and diabetes.
Russian Cardiology and Research Complex, 3-d Cherepkovskaya st., 15a, Moscow, 121552, Russia.
Vadim Z
VZ
Lankin
Alla K
AK
Tikhaze
D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015227:Lipid Peroxidation; D008687:Metformin / Q000494:pharmacology; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D000975:Antioxidants; D005609:Free Radicals; D007004:Hypoglycemic Agents; D008687:Metformin; D005947:Glucose