Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts
- 1 September 1998
- journal article
- research article
- Published by Springer Nature in Nature Medicine
- Vol. 4 (9) , 1025-1031
- https://doi.org/10.1038/2012
Abstract
Accelerated atherosclerosis in patients with diabetes is a major cause of their morbidity and mortality, and it is unresponsive to therapy aimed at restoring relative euglycemia. In hyperglycemia, nonenzymatic glycation and oxidation of proteins and lipids results in the accumulation of irreversibly formed advanced glycation endproducts. These advanced glycation endproducts engage their receptor in cells of the blood vessel wall, thereby activating mechanisms linked to the development of vascular lesions. We report here a model of accelerated and advanced atherosclerosis in diabetic mice deficient for apolipoprotein E. Treatment of these mice with the soluble extracellular domain of the receptor for advanced glycation endproducts completely suppressed diabetic atherosclerosis in a glycemia- and lipid-independent manner. These findings indicate interaction between the advanced glycation endproducts and their receptor is involved in the development of accelerated atherosclerosis in diabetes, and identify this receptor as a new therapeutic target in diabetic macrovascular disease.This publication has 38 references indexed in Scilit:
- The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis.Journal of Clinical Investigation, 1996
- Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats.Journal of Clinical Investigation, 1996
- Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes.Journal of Clinical Investigation, 1995
- Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins.Proceedings of the National Academy of Sciences, 1994
- Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: a link between surface-associated AGEs and diabetic complications.Proceedings of the National Academy of Sciences, 1994
- The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes MellitusNew England Journal of Medicine, 1993
- Glucose and diabetic vascular disease 1The FASEB Journal, 1992
- 5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects.Circulation, 1990
- Advanced Glycosylation End Products in Tissue and the Biochemical Basis of Diabetic ComplicationsNew England Journal of Medicine, 1988
- Diabetes and Cardiovascular DiseaseJAMA, 1979