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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:845.)
© 2006 American Heart Association, Inc.

Vascular Biology

Effect of Rosiglitazone Treatment on Plaque Inflammation and Collagen Content in Nondiabetic Patients

Data From a Randomized Placebo-Controlled Trial

Franz Meisner; Daniel Walcher; Florence Gizard; Xaver Kapfer; Roman Huber; Anja Noak; Ludger Sunder-Plassmann; Helga Bach; Cornelia Haug; Max Bachem; Tatjana Stojakovic; Winfried März; Vinzenz Hombach; Wolfgang Koenig; Bart Staels; Nikolaus Marx

From the Department of Thoracic and Vascular Surgery (F.M., X.K., L.S.-P.), University of Ulm, Germany; Department of Internal Medicine II—Cardiology (D.W., A.N., H.B., V.H., W.K., N.M.), University of Ulm, Germany; UR545 INSERM (F.G., B.S.), Départment d’Athérosclérose, Université de Lille, France; ⁴Department of Neurology (R.H.), University of Ulm, Germany; Department of Clinical Chemistry (C.H., M.B.), University of Ulm, Germany; and Clinical Institute of Medical and Chemical Laboratory Diagnostics (T.S., W.M.), Medical University Graz, Austria.

Correspondence to Nikolaus Marx, MD, Department of Internal Medicine II–Cardiology, University of Ulm, Robert-Koch-Str. 8, D-89081 Ulm, Germany. E-mail nikolaus.marx{at}medizin.uni-ulm.de

Background— Therapeutic strategies to stabilize advanced arteriosclerotic lesions may prevent plaque rupture and reduce the incidence of acute coronary syndromes. Thiazolidinediones (TZDs), like rosiglitazone, are oral antidiabetic drugs with additional antiinflammatory and potential antiatherogenic properties. In a randomized, placebo-controlled, single-blind trial, we examined the effect of 4 weeks of rosiglitazone therapy on histomorphological characteristics of plaque stability in artery specimen of nondiabetic patients scheduled for elective carotid endarterectomy.

Methods and Results— A total of 24 nondiabetic patients with symptomatic carotid artery stenosis were randomly assigned to rosiglitazone (4 mg BID) or placebo in addition to standard therapy. In this population of nondiabetic patients, rosiglitazone treatment did not significantly change fasting blood glucose, fasting insulin, or lipid parameters. In contrast, rosiglitazone significantly reduced CD4-lymphocyte content as well as macrophage HLA-DR expression in the shoulder region, reflecting less inflammatory activation of these cells by lymphocyte interferon-. Moreover, rosiglitazone significantly increased plaque collagen content (7.7±1.6% versus 3.7±0.7% of plaque area; P=0.036) compared with placebo, suggesting that TZD treatment may stabilize arteriosclerotic lesions. In addition, rosiglitazone reduced serum levels of 2 inflammatory arteriosclerosis markers: C-reactive protein and serum amyloid A.

Conclusions— Four weeks of treatment with rosiglitazone significantly reduces vascular inflammation in nondiabetic patients, leading to a more stable type of arteriosclerotic lesion.

The present randomized, placebo-controlled, single-blind trial demonstrates in nondiabetic patients scheduled for carotid endarterectomy that 4 weeks of treatment with rosiglitazone significantly reduces vascular inflammation, leading to a more stable type of arteriosclerotic lesion.

Key Words: plaque • thiazolidinediones • inflammation • collagen • diabetes

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