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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:128.)
© 2009 American Heart Association, Inc.

Clinical and Population Studies

Carotid Atherosclerotic Plaques Stabilize After Stroke

Insights Into the Natural Process of Atherosclerotic Plaque Stabilization

W. Peeters; W.E. Hellings; D.P.V. de Kleijn; J.P.P.M. de Vries; F.L. Moll; A. Vink; G. Pasterkamp

From the Experimental Cardiology Laboratory (W.P., W.E.H., D.P.V.d.K., G.P.), the Department of Vascular Surgery (W.E.H., F.L.M.), and the Department of Pathology (A.V.), University Medical Centre Utrecht; Interuniversity Cardiology Institute of the Netherlands (W.P., D.P.V.d.K.); and the Department of Vascular Surgery (J.P.P.M.d.V.), St. Antonius Hospital, Nieuwegein, The Netherlands.

Correspondence to W. Peeters, MD, Experimental Cardiology Laboratory, Heidelberglaan 100, Room G02-523, PO Box 3584 CX Utrecht, The Netherlands. E-mail w.peeters-2{at}umcutrecht.nl

Objective— Rupture of unstable atherosclerotic plaques is the pathological substrate for acute ischemic events. Underlying cellular and molecular characteristics of plaque rupture have been studied extensively. However, the natural course of symptomatic plaque remodeling after ischemic events is relatively unexplored.

Methods and Results— Atherosclerotic carotid plaques were obtained from 804 symptomatic (stroke=204 and TIA=426) and asymptomatic (n=174) patients undergoing carotid endarterectomy. The presence of macrophages, smooth muscle cells (SMC), collagen, calcification, and lipid-core size were assessed histologically. At protein level, inflammatory mediators (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, interferon-gamma [INF-], tumor necrosis factor-alpha [TNF-], matrix degrading proteinases (MMPs), and an apoptosis marker (caspase-3) were determined. We associated plaque characteristics with time elapsed between the latest event and surgery. Early after stroke and TIA, plaques revealed an unstable phenotype. After stroke, the content of macrophages decreased significantly with time (P=0.02), whereas SMC content tended to increase. At protein level, IL-6, IL-8 expression levels and caspase activity strongly decreased after stroke or TIA.

Conclusions— Symptomatic carotid lesions remodel into more stable plaques over time after stroke. Changes in IL-6 and IL-8 and caspase preceded the decrease of macrophages. These temporal phenotypic plaque alterations should be taken into account for biomarker and therapeutic target validation studies using human atherosclerotic plaques.

The composition of 804 atherosclerotic plaques from patients who underwent carotid endarterectomy has been related to the time, elapsed between the latest cerebrovascular ischemic event and surgical excision. After stroke as well after TIA, the inflammatory status of the plaque decreased independent from potential confounders at histological and protein level.

Key Words: atherosclerosis • carotid arteries • inflammation • plaque • stroke

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