Pathophysiology of oxidative stress in diabetes mellitus.
Oxidative stress is believed to play an important role, albeit not fully recognized, in the development of vascular complications in diabetes mellitus (DM) particularly type 2. In the majority of studies, attention was focused on lipid oxidation, specifically on that of low-density lipoproteins (LDLs). More recent investigations have revealed that it is not only the lipid but also the apolipoprotein moiety of LDL that becomes oxidatively modified resulting in the formation of insoluble aggregates. Consequently, it has been documented that LDL aggregation was due to the hydroxyl radical-induced dityrosine crosslinking between apo B monomers. In DM patients with atherosclerotic complications, intravascular fibrous deposits were shown to contain, in addition to oxidized LDL, a fibrin-like material (FLM). This material is immunologically identical to fibrin that is normally formed as a result of intravascular activation of the blood coagulation cascade. Although DM patients with vascular disease display increased concentration of plasma fibrinogen (Fbg), the precursor of fibrin, no markers of full blown activation of blood coagulation could be found.
Lipinski
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Department of Genetics and Epidemiology, Room 305 Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA. boguslaw_lipinski@joslin.harvard.edu
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000503:physiopathology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology* / Q000517:prevention & control; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*
D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005340:Fibrinogen