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

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• 作者：S ; er 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.
• 关键词：Inflammation ; Atherosclerosis ; Endarterectomy ; Mycophenolate mofetil
• 刊名：Atherosclerosis
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：211
• 期：1
• 页码：231-236
• 全文大小：472 K

文摘

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 profiling 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.