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

Atherosclerosis. 2010 Jul;211(1):231-6. doi: 10.1016/j.atherosclerosis.2010.01.043. Epub 2010 Feb 6.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / drug therapy
  • Atherosclerosis / immunology
  • Atherosclerosis / pathology
  • Carotid Stenosis / drug therapy*
  • Carotid Stenosis / surgery
  • Endarterectomy, Carotid
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • T-Lymphocytes, Regulatory / immunology


  • Immunosuppressive Agents
  • Mycophenolic Acid

Associated data

  • ISRCTN/ISRCTN84092396