Published Online
on December 2, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on September 15, 2004
Revised on October 14, 2004
Accepted on October 20, 2004

Concurrent Treatment With Renin-Angiotensin System Blockers and Acetylsalicylic Acid Reduces Nuclear Factor 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; and 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.

^* To whom correspondence should be addressed. 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 B (NFB) and C-reactive protein (CRP). We hypothesized that the combination of RAS blockers (RASb) and ASA reduces NFB 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 NFB, 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 NFB (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 NFB 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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