Journal Article

Monocyte Gene Expression Signature of Patients with Early Onset Coronary Artery Disease

Krishnan, Unni, Creemers, Esther E., Rendon, Augusto, Trip, Mieke D., Sondermeijer, Brigitte M., Goodall, Alison H., Watkins, Nicholas A., Maiwald, Stepanie, Basart, Hanneke, Sivapalaratnam, Suthesh, Pinto-Sietsma, Sara J., Ouwehand, Willem H., Hovingh, Kees, Kastelein, John J. P.

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ABCA1 protein / Adult / Arteriosclerosis / Aspirin / Aspirin - pharmacology / Aspirin - therapeutic use / Atherosclerosis / ATP-binding protein / B cells / Biology / Biomedical research / Birth defects / Cardiovascular disease / Cardiovascular diseases / Case-Control Studies / Celiac disease / Coronary artery / Coronary artery disease / Coronary Artery Disease - drug therapy / Coronary Artery Disease - genetics / Coronary Artery Disease - pathology / Coronary heart disease / Coronary vessels / Development and progression / Diabetes / Gene expression / Gene Expression Profiling / Gene Expression Regulation - drug effects / Gene loci / Genes / Genetics / Genomes / Genomics / GSTM1 protein / Health aspects / Health services / Heart diseases / Hematology / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Male / Medicine / Melanoma / Monocytes / Monocytes - drug effects / Monocytes - metabolism / Pathogenesis / Pathways / Patients / Polymerase Chain Reaction / Reproducibility of Results / Risk analysis / Risk factors / Risk management / Simvastatin / Smoking / Statins / Therapeutic applications / Thrombosis / Type 2 diabetes / Vascular diseases / Vitamin B