Abstract 18432: Global Transcriptional Profiling of Monocytes and Macrophages and Association with Coronary Artery Disease Risk Factors in a Large Multi-Center Collaborative Study: The Cardiogenics Transcriptomic Study
Objective: Global transcriptional profile of cells involved in the pathogenesis of coronary artery disease (CAD) is poorly characterized. We thus aimed to identify biological processes and transcription factors (TFs) accompanying the transition of monocytes to macrophages as well as expression patterns associated to CAD risk factors.
Methods: Within Cardiogenics Consortium, we recruited 459 CAD patients and 458 healthy subjects. Most CAD patients had a validated MI within the previous 3-36 months and were aged between 40 and 65 years. Healthy subjects were all blood donors (42% male), without history of CAD. 1,533 RNA samples (849 monocytes and 684 macrophages) from the 917 subjects were analyzed on the Illumina Ref-8 v3.0 arrays.
Results: Monocyte to macrophages differentiation process involves massive changes in gene expression with 4.181 genes being significantly (P<10-3) modulated. Overall, this process is characterized by repression of large numbers of genes involved in the immune response and over-expression of genes of the lipid metabolism. Specifically, multiple genes expressed only in macrophages are involved in cholesterol metabolism such as APOE, PLAU, A2M, and SPP1. We found 155 TFs being significantly modulated between monocytes and macrophages. Among which 84.5% were down-regulated in macrophages. We found 28 and 14 genes being associated with gender in monocyte and macrophages, respectively. In monocytes, the expression of 21 genes was associated with BMI, including genes involved in cholesterol, steroid and lipid metabolic processes such as ABCG1, YWHAH, SARD5A1, and SORT1, and genes involved in obesity such as ADRB2 and GPX3. Only two genes, NEFH and AGPAT4 were found to be associated with age in monocytes.
Conclusions: We provide the first comprehensive large-scale analyses of monocyte and macrophage transcriptomes. The finding that multiple genes of the lipid system were over-expressed in macrophages is not only concordant with the fact that these cells are essential modulators of lipid metabolism but shows that macrophages express lipid handling genes even in the absence of exposure to exogenous lipids. Our results might be used to interpret GWAS finding and shed light on the role of monocyte and macrophage cells in CAD.
- © 2011 by American Heart Association, Inc.