How hyperglycemia promotes atherosclerosis: molecular mechanisms

Author(s): Aronson D, Rayfield EJ


Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease. Atherosclerosis accounts for virtually 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized a major factor in the pathogenesis of atherosclerosis in diabetes. Hyperglycemia induces a large number of alterations at the cellular level of vascular tissue that potentially accelerate the atherosclerotic process. Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: 1) Nonenzymatic glycosylation of proteins and lipids which can interfere with their normal function by disrupting molecular conformation, alter enzymatic activity, reduce degradative capacity, and interfere with receptor recognition. In addition, glycosylated proteins interact with a specific receptor present on all cells relevant to the atherosclerotic process, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells. The interaction of glycosylated proteins with their receptor results in the induction of oxidative stress and proinflammatory responses 2) oxidative stress 3) protein kinase C (PKC) activation with subsequent alteration in growth factor expression. Importantly, these mechanisms may be interrelated. For example, hyperglycemia-induced oxidative stress promotes both the formation of advanced glycosylation end products and PKC activation.

Similar Articles

DNA repair, genome stability, and aging

Author(s): Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, et al.

A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes

Author(s): Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, et al.

Type 2 diabetes as an inflammatory disease

Author(s): Donath MY, Shoelson SE

Orally delivered microencapsulated live probiotic formulation lowers serum lipids in hypercholesterolemic hamsters

Author(s): Bhathena J, Martoni C, Kulamarva A, Urbanska AM, Malhotra M, et al.

Lactobacillus fermentum NCIMB 5221 has a greater ferulic acid production compared to other ferulic acid esterase producing Lactobacilli

Author(s): Tomaro-Duchesneau C, Saha S, Malhotra M, Coussa-Charley M, Al-Salami H, et al.

Impact of Recent Increase in Incidence on Future Diabetes Burden: U.S., 2005-2050

Author(s): Narayan KM, Boyle JP, Geiss LS, Saaddine JB, Thompson TJ

Screening of Lactic Acid Bacteria for Bile Salt Hydrolase Activity

Author(s): Tanaka H, Doesburg K, Iwasaki T, Mierau I

Ferulic Acid: therapeutic potential through its antioxidant property

Author(s): Srinivasan M, Sudheer AR, Menon VP

Protective effects of ferulic acid on hyperlipidemic diabetic rats

Author(s): Balasubashini MS, Rukkumani R, Menon VP

Ferulic acid alleviates lipid peroxidation in diabetic rats

Author(s): Balasubashini MS, Rukkumani R, Viswanathan P, Menon VP

Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells

Author(s): Chang CJ, Chiu JH, Tseng LM, Chang CH, Chien TM, et al.

Glycosylated hemoglobins and long-term blood glucose control in diabetes mellitus

Author(s): Gabbay KH, Hasty K, Breslow JL, Ellison RC, Bunn HF, et al.