Mycophenolate mofetil attenuates plaque inflammation in patients with symptomatic carotid artery stenosis

Sander I. van Leuven, Diederik F. van Wijk, Oscar L. Volger, Jean-Paul P. M. de Vries, Chris M. van der Loos, Dominique V. P. de Kleijn, Anton J. G. Horrevoets, Paul P. Tak, Allard C. van der Wal, Onno J. de Boer, Gerard Pasterkamp, Michael R. Hayden, John J. P. Kastelein, Erik S. Stroes

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Abstract

Atherosclerosis as well as the subsequent progression towards cardiovascular events are considered to, at least partially, be a consequence of chronic inflammatory activity. Therefore, we decided to evaluate the impact of short-term immunosuppressive treatment on plaque characteristics in patients with symptomatic carotid artery stenosis. Twenty-one patients were randomized to receive either 1000 mg. Mycophenolate mofetil (MMF) BD or placebo for at least 2 weeks prior to undergoing carotid endarterectomy (CEA). The serial sections of the CEA specimens were immunostained for activated T-cells (CD3(+)CD69(+)), regulatory T-cells (CD3(+)FOXP3(+)) and macrophages (CD68). In addition, gene expression pro. ling was performed by Illumina gene-array. Immunostaining revealed a reduction of activated T-cells in nine MMF-treated patients compared to 11 placebo-treated control patients (19.7% vs. 28.1%; p <0.05) as well as an increase of regulatory T-cells (3.8% vs. 1.8%; p = 0.05). Microarray analyses confirmed beneficial changes to plaque phenotype, showing reduced expression of pro-inflammatory genes. Significantly reduced expression of metalloproteinases and osteopontin was observed in three out of nine MMF-treated patients compared to nil out of 11 in the placebo group. In the present study we show that immunosuppressive treatment for two-and-a-half weeks prior to CEA elicits changes in the plaque phenotype of symptomatic patients. These changes include reduced inflammatory cell presence with a concomitant decrease in pro-inflammatory gene expression. (C) 2010 Elsevier Ireland Ltd. All rights reserved
Original languageEnglish
Pages (from-to)231-236
JournalAtherosclerosis
Volume211
Issue number1
DOIs
Publication statusPublished - 2010

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