on November 11, 2002
Circulation. 2002
Published online before print November 11, 2002, doi: 10.1161/01.CIR.0000039325.03698.36
Published online before print November 11, 2002, doi: 10.1161/01.CIR.0000039325.03698.36
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Submitted on June 13, 2002
From the Division of Surgical Science, Department of Surgery (L.G.B., T.W., W.Q., Y.L., L.R., M.T.G., B.M., T.K., D.C.L., Y.K., D.M.S., A.M.S.); Department of Physiology & Cellular Biophysics (D.M.S.), College of Physicians & Surgeons; and Division of Periodontics, School of Dental & Oral Surgery (E.L.), Columbia University, New York, NY. * To whom correspondence should be addressed. E-mail: ams11{at}columbia.edu.
Background—Previous studies suggested that blockade of RAGE in diabetic apolipoprotein (apo) E-null mice suppressed early acceleration of atherosclerosis. A critical test of the potential applicability of RAGE blockade to clinical settings was its ability to impact established vascular disease. In this study, we tested the hypothesis that RAGE contributed to lesion progression in established atherosclerosis in diabetic apoE-null mice. Methods and Results—Male apoE-null mice, age 6 weeks, were rendered diabetic with streptozotocin or treated with citrate buffer. At age 14 weeks, certain mice were killed or treated with once-daily murine soluble RAGE or albumin; all mice were killed at age 20 weeks. Compared with diabetic mice at age 14 weeks, albumin-treated animals displayed increased atherosclerotic lesion area and complexity. In diabetic mice treated with sRAGE from age 14 to 20 weeks, lesion area and complexity were significantly reduced and not statistically different from those observed in diabetic mice at age 14 weeks. In parallel, decreased parameters of inflammation and mononuclear phagocyte and smooth muscle cell activation were observed. Conclusions—RAGE contributes not only to accelerated lesion formation in diabetic apoE-null mice but also to lesion progression. Blockade of RAGE may be a novel strategy to stabilize atherosclerosis and vascular inflammation in established diabetes.
Revised on August 23, 2002
Accepted on August 24, 2002
RAGE Blockade Stabilizes Established Atherosclerosis in Diabetic Apolipoprotein E-Null Mice
Loredana G. Bucciarelli MD,
Key words: diabetes mellitus • inflammation • muscle, smooth • atherosclerosis
Related Article:
Circulation 2002 106: 2760-2763.
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