Hyperglycemia can increase oxidative stress through several pathways. Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein. Indeed, there are strong correlations between levels of glycoxidation products in skin collagen and the severity of diabetic retinal, renal, and vascular disease [ 68 , 69 ].
Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease CAD , stroke, and peripheral arterial disease [ 1 — 3 ]. Glucosylation of low-density lipoproteins to an extent comparable to that seen in diabetes slows their catabolism. Pathogenesis of the atherosclerotic lesion. Prolonged exposure to hyperglycemia is now recognized as the primary casual factor in the pathogenesis of diabetic complications [ 4 — 6 ].
Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: Glycated tau protein in Alzheimer disease: Mechanism of autoxidative glycosylation: Oxidation reactions occur normally during glycation can oxidize the amine-containing phospholipids component of LDL, independently of transition metals or exogenous free radical-generating systems [ 19 ].
Normalization of diacylglycerol-protein kinase C activation by vitamin E in aorta of diabetic rats and cultured rat smooth muscle cells exposed to elevated glucose levels. The potential role of RAGE in the atherogenic process in diabetes has been demonstrated by Park and associates [ 43 ].
Table 1 Atherosclerosis promoting effects of AGEs: Indeed, there are strong correlations between levels of glycoxidation products in skin collagen and the severity of diabetic retinal, renal, and vascular disease. Ascorbic acid metabolism and polyol pathway in diabetes.
Reduced glutathione content [ 58 , 59 ], as well as reduced vitamin E [ 60 , 61 ] have been reported in diabetic patients.
Witztum Diabetes 1984. Oxidants produced in the setting of hyperglycemia can activate PKC [ 70 ]. Abstract Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease CAD , stroke, and peripheral arterial disease.
The development of vascular was more rapid with the formation of more complex lesions fibrous caps, extensive monocyte infiltration, etc and atherosclerosis extending distally in the aorta and major arteries. The degree of nonenzymatic glycation is determined mainly by the glucose concentration and time of exposure.
With increased permeability of endothelial cell monolayers [ 34 , 35 ]. Enhanced synthesis of extracellular matrix components [ 10 ].
Cellular receptors for advanced glycation end products.