title: Monocyte gene expression signature of patients with early onset coronary artery disease.
abstract: The burden of cardiovascular disease (CVD) cannot be fully addressed by therapy targeting known pathophysiological pathways. Even with stringent control of all risk factors CVD events are only diminished by half. A number of additional pathways probably play a role in the development of CVD and might serve as novel therapeutic targets. Genome wide expression studies represent a powerful tool to identify such novel pathways. We compared the expression profiles in monocytes from twenty two young male patients with premature familial CAD with those from controls matched for age, sex and smoking status, without a family history of CVD. Since all patients were on statins and aspirin treatment, potentially affecting the expression of genes in monocytes, twelve controls were subsequently treated with simvastatin and aspirin for 6 and 2 weeks, respectively. By whole genome expression arrays six genes were identified to have differential expression in the monocytes of patients versus controls; ABCA1, ABCG1 and RGS1 were downregulated in patients, whereas ADRB2, FOLR3 and GSTM1 were upregulated. Differential expression of all genes, apart from GSTM1, was confirmed by qPCR. Aspirin and statins altered gene expression of ABCG1 and ADBR2. All finding were validated in a second group of twenty four patients and controls. Differential expression of ABCA1, RSG1 and ADBR2 was replicated. In conclusion, we identified these 3 genes to be expressed differently in CAD cases which might play a role in the pathogenesis of atherosclerotic vascular disease.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. s.sivapalaratnam@amc.uva.nl
authors.forename: Suthesh
authors.initials: S
authors.lastname: Sivapalaratnam
authors.forename: Hanneke
authors.initials: H
authors.lastname: Basart
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Stepanie
authors.initials: S
authors.lastname: Maiwald
authors.forename: Augusto
authors.initials: A
authors.lastname: Rendon
authors.forename: Unni
authors.initials: U
authors.lastname: Krishnan
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Sondermeijer
authors.forename: Esther E
authors.initials: EE
authors.lastname: Creemers
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Pinto-Sietsma
authors.forename: Kees
authors.initials: K
authors.lastname: Hovingh
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.forename: Mieke D
authors.initials: MD
authors.lastname: Trip
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001241:Aspirin