Complement expression in human atherosclerotic plaques and blood cells in patients with coronary artery disease
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Background
Inflammatory processes are a key cause of atherosclerosis and cardiovascular diseases. Complement system has been implicated but evidence is less clear. We tested whether atherosclerosis severity, plaque types, and vascular region are associated with mRNA expression of genes encoding proteins of the complement system and investigated the cell-specific expression of the most differentially expressed transcripts in plaque macrophages, fibroblasts, and endothelial, smooth muscle, Schwann, mast, plasma, T-, and B-cells.
Methods
Total mRNA was isolated, and gene expression analyzed from 29 carotid, 15 abdominal aortic, and 24 femoral plaque samples, and 28 atherosclerosis-free control left internal thoracic artery samples of 95 patients, as well as from 97 whole blood and 97 peripheral mononuclear cell samples of 97 patients. Genome-wide transcriptomic analyses were done using RNA bead microarray platforms. Differential expression was compared between plaques with normal arteries, unstable with stable plaques, as well as CAD patients with CAD-free patients.
Results
A total of 33 out of 90 (37%) transcripts of the complement system were differentially expressed in atherosclerotic plaques as compared to histologically normal arteries. In aortic, carotid, and femoral plaques 38, 36 and 29 transcripts, respectively, were differentially expressed, of which 25 were shared by the plaques of all arterial beds. Among the most interesting gene-level findings, we observed that transcripts of the integrin gene ITGB2 are highly upregulated mostly in macrophages and T cells while having top centrality in the network and top enriched genesets related to cell junctions.
Conclusions
This is the first study exploring the association of local complement expression across multiple arterial beds and histologically diverse plaque samples. The local effect of complement-mediated inflammation is indicated in inflammatory plaque tissue but not in smooth muscle cell-dominated plaques. Taken together, gene expression of the complement system components in artery cells is associated with advanced atherosclerosis.
