doi: 10.1161/01.RES.0000259589.34348.74
© 2007 American Heart Association, Inc.
Reviews |
Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques?
From the Departments of Pathology (J.E.K., F.J., K.E.B.) and Medicine (R.C.L.), University of Washington, Seattle.
Correspondence to K.E. Bornfeldt, Department of Pathology, 1959 NE Pacific St, University of Washington, Seattle, WA 98195-7470. E-mail bornf{at}u.washington.edu
This Review is part of a thematic series on Atherosclerosis in Diabetes: Dyslipidemia Versus Hyperglycemia, which includes the following articles:
Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques?
The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis
Recipes for Creating Animal Models of Diabetic Cardiovascular Disease
Lipids, Glucose, and Oxidative Reactions in Diabetes and Atherosclerosis
Karin E. Bornfeldt Guest Editor
It is becoming increasingly clear that suboptimal blood glucose control results in adverse effects on large blood vessels, thereby accelerating atherosclerosis and cardiovascular disease, manifested as myocardial infarction, stroke, and peripheral vascular disease. Cardiovascular disease is accelerated by both type 1 and type 2 diabetes. In type 1 diabetes, hyperglycemia generally occurs in the absence of elevated blood lipid levels, whereas type 2 diabetes is frequently associated with dyslipidemia. In this review article, we discuss hyperglycemia versus hyperlipidemia as culprits in diabetes-accelerated atherosclerosis and cardiovascular disease, with emphasis on studies in mouse models and isolated vascular cells. Recent studies on LDL receptor–deficient mice that are hyperglycemic, but exhibit no marked dyslipidemia compared with nondiabetic controls, show that diabetes in the absence of diabetes-induced hyperlipidemia is associated with an accelerated formation of atherosclerotic lesions, similar to what is seen in fat-fed nondiabetic mice. These effects of diabetes are masked in severely dyslipidemic mice, suggesting that the effects of glucose and lipids on lesion initiation might be mediated by similar mechanisms. Recent evidence from isolated endothelial cells demonstrates that glucose and lipids can induce endothelial dysfunction through similar intracellular mechanisms. Analogous effects of glucose and lipids are also seen in macrophages. Furthermore, glucose exerts many of its cellular effects through lipid mediators. We propose that diabetes without associated dyslipidemia accelerates atherosclerosis by mechanisms that can also be activated by hyperlipidemia.
Key Words: Atherosclerosis • Diabetes • Fatty acids • Glucose • Mouse models
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