Table 4.
Gene | Function and Relation to AAA or Atherosclerosis | FC | p-Value | Location | Vascular Gene Set |
---|---|---|---|---|---|
CXCL13 C-X-C motif chemokine 13 |
Selective chemotactic for B cells (B-1 and B-2 subsets), by interacting with chemokine receptor CXCR5. Control of B cell organization within follicles of lymphoid tissues [25,26,27]. High levels of CXCL13 are found in aneurysm and in atherosclerotic lesions |
32.26 | 1.12 × 10−4 | Extracellular space | YES |
COL11A1 Collagen alpha-1(XI) chain |
Adds structure and strength to connective tissues supporting muscles, joints, organs, and skin. Col11a1 protein levels are upregulated in TAA and AAA tissue [23,28,29]. |
27.05 | 5.29 × 10−5 | Extracellular space | YES |
SAA2 Serum amyloid A protein |
Production primarily in liver, circulates in low levels in the blood. Although its function is not fully understood, serum amyloid A appears to play a role in the immune system. Different biomarker studies have shown association of SAA with atherosclerotic disease. Patients with atherosclerotic disease show increased levels of Amyloid A protein [30,31,32,33]. |
24.96 | 3.95 × 10−7 | Extracellular space | NO |
ADIPOQ Adiponectin |
Involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in liver and skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Negatively regulates TNF-alpha expression in various tissues such as liver and macrophages. Inhibits endothelial NFκB signaling through a cAMP-dependent pathway. Adiponectin is dysregulated in aneurysm and atherosclerotic disease [34,35,36]. |
21.45 | 3.01 × 10−4 | Extracellular space | YES |
FDCSP follicular dendritic cell-secreted protein |
FDCSP bind to the surface of B-lymphoma cells. Functions as a secreted mediator acting upon B-cells. No direct associations of FDCSP with atherosclerotic disease or AAA are described in literature [37,38]. |
21.38 | 1.01 × 10−4 | Extracellular space | NO |
POU2AF1 POU domain class 2-associating factor 1 |
Transcriptional coactivator that specifically associates with either OCT1 or OCT2. It boosts the OCT1 mediated promoter activity and to a lesser extent that of OCT2. Essential for the response of B-cells to antigens and required for the formation of germinal centers. Little is known about this factor in AAA, though in carotid plaque formation analysis it is shown that POU2AF1 is upregulated, which is related to the immune and inflammatory processes linked to atherosclerosis [39,40]. |
18.84 | 4.79 ×10−4 | Nucleus | NO |
MS4A1 membrane-spanning 4A/CD20 |
B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. B-lymphocytes with MS4A1 expressed are found in aneurysm and atherosclerotic [41,42,43,44]. |
18.41 | 2.61 × 10−4 | Plasma membrane | YES |
MZB1 Marginal zone B and B1 cell-specific protein |
Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion. Acts as a hormone-regulated adipokine/ proinflammatory cytokine implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes. No direct association of MZB1 with atherosclerotic disease or AAA are described in literature [45]. |
17.07 | 1.26 × 10−3 | Extracellular space | NO |
SLC7A5 Solute carrier family 7 member 5 |
Encodes for a protein called y+L amino acid transporter 1 (y+LAT-1). Involved in transport of amino acids, namely lysine, arginine, and ornithine. The y+LAT-1 protein forms one part (the light subunit) of a complex called the heterodimeric cationic amino acid transporter, responsible for binding to the amino acids that are transported. There is no direct association of SLC7A5 with atherosclerotic disease or AAA described in the literature [46]. |
15.72 | 5.37 × 10−7 | Plasma membrane | YES |
LEP Leptin |
Hormone involved in the regulation of body weight. As fat accumulates in cells, more leptin is produced, indicating that fat stores are increasing. Increased leptin levels are associated with atherosclerotic disease. Furthermore, in an AAA animal model mRNA and protein levels of leptin were found to be upregulated in aneurysmatic tissue [47,48,49,50,51]. |
14.29 | 1.94 × 10−6 | Extracellular space | YES |