201909211025頸動脈硬化衰減治療劑 Mycophenolate mofetil免疫抑制 抗發炎2017-2019

Mycophenolate mofetil免疫抑制 抗發炎 attenuates衰減 plaque inflammation in patients with symptomatic carotid artery stenosis.

Source

Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.i.vanleuven@amc.uva.nl

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 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.

Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

PMID:
20202636
[PubMed - indexed for MEDLINE]

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