title: Mycophenolate mofetil attenuates plaque inflammation in patients with symptomatic carotid artery stenosis.
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.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.i.vanleuven@amc.uva.nl
authors.forename: Sander I
authors.initials: SI
authors.lastname: van Leuven
authors.forename: Diederik F
authors.initials: DF
authors.lastname: van Wijk
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Volger
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Dominique V P
authors.initials: DV
authors.lastname: de Kleijn
authors.forename: Anton J G
authors.initials: AJ
authors.lastname: Horrevoets
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Erik S
authors.initials: ES
authors.lastname: Stroes
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid