Relationship of Glycemia to Cardiovascular Disease ... - Lipids Online

The Proinflammatory Milieu in Atheromata
Is Mediated by RAGEs in Diabetes Mellitus
RAGE = receptor for advanced glycosylated end-products
Reprinted from Cipollone F, et al. Circulation. 2003;108:1070–1077,
with permission from Lippincott Williams & Wilkins.
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The Proinflammatory Milieu in Atheromata Is Mediated by RAGEs in Diabetes
Mellitus
In this study by Cipollone et al., carotid endarterectomy specimens from diabetic patients
were found to be distinctly different from those of nondiabetic patients. This study also
provided in-vivo data demonstrating that atheromata in diabetic patients may have a
different pathobiology. The diabetic carotid atheroma specimens contained localized
dense infiltrates of mononuclear cells expressing surface markers consistent with active
inflammation. The specimens from the nondiabetic patients did not show this degree of
inflammatory infiltrate. Monocytes, macrophages, and lymphocytes reside in this region
of the plaque because the receptors for advanced glycosylated end-products (RAGEs) are
located in these areas, and the attachment of the RAGEs to the receptor induces a
chemotactic response accounting for the inflammatory appearance of atheroma
specimens from diabetic patients. Furthermore, the density of the RAGEs was related to
the level of glycemia in these particular patients, thus providing a link between glycemia
and vascular inflammation. The specimens from the diabetic patients expressed high
concentrations of matrix metallinoproteinases in the area of inflammatory cells, but those
of the nondiabetic patients did not.
Let us now examine the possibility that the pharmacologic strategies used to lower
glucose in both prediabetes and diabetes can reduce the risk of cardiovascular disease.
Reference:
Cipollone F, Iezzi A, Fazia M, et al. The receptor RAGE as a progression factor
amplifying arachidonate-dependent inflammatory and proteolytic response in human
atherosclerotic plaques: role of glycemic control. Circulation. 2003;108:1070-1077.
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© 2009 Baylor College of Medicine, Houston, Texas