Mycophenolate mofetil attenuates plaque inflammation in patients with symptomatic carotid artery stenosis.
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.
van Leuven
Sander I
SI
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.i.vanleuven@amc.uva.nl
van Wijk
Diederik F
DF
Volger
Oscar L
OL
de Vries
Jean-Paul P M
JP
van der Loos
Chris M
CM
de Kleijn
Dominique V P
DV
Horrevoets
Anton J G
AJ
Tak
Paul P
PP
van der Wal
Allard C
AC
de Boer
Onno J
OJ
Pasterkamp
Gerard
G
Hayden
Michael R
MR
Kastelein
John J P
JJ
Stroes
Erik S
ES
D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000601:surgery; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid