Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

Abstract

Background Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. Methodology/Principal Findings We characterized the genes generally involved in human advanced atherosclerotic (AHA type V–VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). Conclusions This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds.

Kindlin 3 (FERMT3) is associated with unstable atherosclerotic plaques, anti-inflammatory type II macrophages and upregulation of beta-2 integrins in all major arterial beds

“…Both arrays were run according to given instructions by the manufacturer and scanned with the Illumina iScan system. More detailed descriptions of the methodology and qRT-PCR validation of the microarrays have been published previously [27,28].…”

Smooth muscle cells in human atherosclerosis: Proteomic profiling reveals differences in expression of Annexin A1 and mitochondrial proteins in carotid disease

“…In order to eliminate the possibility that changes in the molecules of interest were due to the culture conditions, we verified their gene expression in the Tampere Vascular Study cohort [8]. Patient characteristics relative to the Tampere Vascular Study are presented in Supplemental Table SII.…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…Novel atherosclerotic markers indicating neutrophil activation represent Lf, an innate immune system protein with antiinflammatory and antioxidant properties [549,550] . Immunohistochemical staining of Lf was found in advanced human atherosclerotic carotid artery, as well as its co-localization with neutrophils and T and B lymphocytes in aortic plaques [551] . Lf appeared to be one of nine genes specifically induced predominantly in atherosclerotic aortic plaques [551] .…”

“…Immunohistochemical staining of Lf was found in advanced human atherosclerotic carotid artery, as well as its co-localization with neutrophils and T and B lymphocytes in aortic plaques [551] . Lf appeared to be one of nine genes specifically induced predominantly in atherosclerotic aortic plaques [551] . Lf, a natural defense iron-binding protein is produced and secreted by glandular epithelial cells and circulating polymophonuclear neutrophils, and found mainly in milk, saliva, mucosal and other secretory fluids, has been found to possess antiinflammatory, antibacterial, antiparasitic, antimycotic, antiviral, and antineoplastic activity [552,553] .…”