title: Irreversibly glycated albumin alters the physico-chemical characteristics of low density lipoproteins of normal and diabetic subjects.
abstract: In diabetic plasma, glycated albumin and glycated LDL coexist with augmented levels of peroxides, conditions frequently associated with the development of accelerated atherosclerosis. The direct interaction between irreversibly glycated albumin, LDL and oxidation have not been explored yet. We tried to elucidate whether irreversibly glycated albumin (AGE-Alb) induces changes in the chemistry and morphology of LDL particle, and if AGE-Alb has the ability to scavenge free radicals, as reported for native albumin. LDL isolated from normal (nLDL) or diabetic human subjects (dLDL) was incubated in vitro with AGE-Alb in conditions of autoxidation (37 degrees C, 24-48 h in the absence of oxidation inhibitors) or of Cu2+ induced-oxidation. The results showed that, especially in the latter condition, AGE-Alb induced marked physico-chemical modifications of both nLDL and dLDL without significant changes in the level of peroxides. Incubation with AGE-Alb decreased the cholesteryl esters/unesterified cholesterol ratio of nLDL by 30% and of dLDL by approximately 50%. Concomitantly, in oxidative conditions a marked increase (approximately 3-fold) in the lysophosphatidylcholine/phosphatidylcholine ratio of dLDL was detected. Apolipoprotein B integrity as well as the morphology of the lipoprotein particles were drastically affected. To a lesser extent, these modifications occurred also in the presence of inhibitors of oxidation at 37 degrees C, but not at 4 degrees C. The above described effects were constantly more pronounced in the case of dLDL. These results indicated that in the absence of other plasma or vascular tissue components (e.g., endothelial cells, extracellular matrix) AGE-Alb by itself induces alterations in the chemistry and morphology of LDL, especially of glycated LDL, modifications that may account for the occurrence of accelerated atherogenesis in diabetes.
authors: Institute of Cellular Biology and Pathology, Bucharest, Romania.
authors: A
authors: A
authors: Dobrian
authors: M
authors: M
authors: Simionescu
mesh_terms: D001161:Arteriosclerosis / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry* / Q000648:ultrastructure; D012709:Serum Albumin / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D000093423:Glycated Serum Albumin; D000093844:Glycated Proteins
chemical_list: D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D012709:Serum Albumin; D017392:Thiobarbituric Acid Reactive Substances; D000093423:Glycated Serum Albumin; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins