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Stroke. 2005;36:14-20
Published online before print December 2, 2004, doi: 10.1161/01.STR.0000150643.08420.78
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(Stroke. 2005;36:14.)
© 2005 American Heart Association, Inc.


Original Contributions

Concurrent Treatment With Renin-Angiotensin System Blockers and Acetylsalicylic Acid Reduces Nuclear Factor {kappa}B Activation and C-Reactive Protein Expression in Human Carotid Artery Plaques

Katherine J.E. Sattler, MD; Julie E. Woodrum, MS; Offer Galili, MD; Monica Olson, BS; Saquib Samee, MD; Fredric B. Meyer, MD; Xiang-Yang Zhu, MD; Lilach O. Lerman, MD, PhD Amir Lerman, MD

From the Divisions of Cardiovascular Diseases, Nephrology, and Hypertension (K.J.E.S., J.E.W., O.G., M.O., S.S., A.L., X.-Y.Z., L.O.L.), Department of Internal Medicine; and the Department of Neurosurgery (F.B.M.), Mayo Clinic Rochester, Minn.

Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905. E-mail lerman.amir{at}mayo.edu

Background and Purpose— The local renin-angiotensin system (RAS) and cyclooxygenase-2 contribute to the activation of nuclear factor {kappa}B (NF{kappa}B) and C-reactive protein (CRP). We hypothesized that the combination of RAS blockers (RASb) and ASA reduces NF{kappa}B and CRP within atherosclerotic plaques.

Methods— Patients undergoing carotid endarterectomy were divided into groups according to treatment (RASb–acetylsalicylic acid [ASA], ASA, RASb, and control). The expression of NF{kappa}B, CRP, and CD40L was analyzed through Western blots in the obtained plaques.

Results— Plaques from patients treated with the combination of RASb and ASA showed lower expression of NF{kappa}B (25.4±9.8 densitometric units [DU]) than those of the control group (57.6±13.2 DU, P=0.03) as well as lower expression of CRP (20.9±9.6 DU) than those of the other treatment groups (ASA 86.1±13 DU, RASb 88.4±31 DU, controls 67.8±18.6, P=0.004). A negative expression of NF{kappa}B was associated with a reduced incidence of symptoms compared with a positive expression (5/33 [15.1%] versus 14/35 [40%], P=0.031).

Conclusions— The combined treatment with RASb and ASA decreases the expression of inflammatory markers in atherosclerosis in humans. This study supports the role of the local RAS and cyclooxygenase-2 in the progression of atherosclerosis.


Key Words: aspirin • atherosclerosis • carotid endarterectomy • growth factors • inflammation




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