The mystery of diabetes and atherosclerosis: time for a new plot.
Most patients with diabetes die from macrovascular complications. Little is known about the pathogenesis of diabetic vascular disease, but recent advances in molecular genetics and oxidation chemistry provide clues to the mystery of diabetes and atherosclerosis. Genetic variants of well-known proteins such as lipoprotein lipase and apolipoprotein E are common. These proteins are suitable candidates for mediating diabetic vascular risk because their variants can produce hypertriglyceridemia, a risk factor for atherosclerosis in diabetes. However, mutations could have different effects on lipoprotein flux across arteries depending on whether expression is dominant in the vascular space or the vascular wall. Lipoproteins retained in the arterial wall are subject to oxidative modification, which could be dependent on glycoxidation, the enzyme myeloperoxidase, or reactive nitrogen species derived from nitric oxide. Accelerated vascular disease in diabetes is likely the result of complex interactions between metabolic derangements such as hyperglycemia, mutations in genes controlling lipid metabolism, and antioxidant defense mechanisms.
Semenkovich
C F
CF
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. semenkov@visar.wustl.edu
Heinecke
J W
JW
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000235:genetics / Q000401:mortality / Q000503:physiopathology*; D064429:Fatty Acid Synthases / Q000235:genetics; D014644:Genetic Variation; D006023:Glycoproteins; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008074:Lipoproteins / Q000378:metabolism; D012307:Risk Factors
D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008074:Lipoproteins; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase