Table 1.
Summary of the published human studies on novel biomarkers (2008–2014) in AAA and their clinical value.
| Category | Biomarker | Author | Year | Study design | Findings | Clinical value |
|---|---|---|---|---|---|---|
| Biomarkers related to cellular signaling pathways | CRP | De Haro et al. [29] | 2012 | Cohort study | A statistical association was confirmed between the AAA diameter and high sensitive-CRP (hs-CRP) plasma levels. Other studies show controversial results [27, 28] | Aneurysm progression |
| sTWEAK | Martín-Ventura et al. [35] |
2011 | Case control study | sTWEAK plasma levels in patients with AAA compared with healthy subjects. sTWEAK concentrations were negatively associated with AAA size and AAA expansion rate | Aneurysm detection and progression | |
|
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| Biomarkers related to circulating cells and inflammation | Lymphocyte correlated biomarkers | Yin et al. [42] | 2010 | Prospective study | CD4(+), CD25(+), and FOXP3(+) T cells in AAA patients are found significantly lower than those of the control group | Aneurysm detection |
| Monocyte-related biomarkers | Ghigliotti et al. [45] | 2013 | Case control study | CD16(+) monocyte subsets were found increased in large abdominal aortic aneurysms and were differentially related to circulating and cell-associated (CD143) biochemical and inflammatory biomarkers | Aneurysm size | |
| Progenitor Cells | Van Spyk et al. [46] | 2013 | Case control study | A lower percentage of CD34(+) cells in AAA patients, compared to PVD patients, was found | Aneurysm detection | |
| Lymphangiogenesis | Scott et al. [47] | 2013 | Case control study | Lymphatic vessel involvement in AAA disease, associated with the extent of inflammation | Aneurysm genesis | |
| Sano et al. [48] | 2014 | Case control study | Infiltration of macrophages in intima/media is associated with lymphangiogenesis and angiogenesis in AAA, while there is evidence of inadequate lymph-drainage in the AAA wall | |||
| Catalase (PMNs) | Ramos-Mozo et al. [49] | 2011 | Case control study | Diminished catalase expression and activity were observed in PMNs from AAA patients compared with controls | Aneurysm detection | |
| Pathogens | Delbosc et al. [50] | 2011 | Experimental study | P. gingivalis accelerates AAA progression via recruitment and activation of neutrophils, leading to production of NETs | Aneurysm generis | |
|
| ||||||
| Proteins released by intraluminal thrombus (ILT) | IGFs | Lindholt et al. [40] | 2011 | Prospective study | Serum IGF-I correlated positively with AAA size and growth rate | Aneurysm size and progression |
| Ramos-Mozo et al. [41] | 2012 | Case control study | IGFBP-1 concentrations were significantly higher in large AAA patients compared with control subjects | Aneurysm size and thrombus existence | ||
| NGAL | Ramos-Mozo et al. [38] | 2012 | Case control study | AAA patients secreted significantly greater amounts of NGAL than PMNs from controls and correlated with retrospective AAA growth | Aneurysm detection and progression | |
| Peroxiredoxin-1 | Martinez-Pinna et al. [36] |
2011 | Prospective study | Increased PRX-1 serum levels in AAA patients compared with healthy subjects and positive correlation among PRX-1 and AAA diameter and expansion rate were also found |
Aneurysm detection and progression | |
|
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| Biomarkers related to extracellular matrix homeostasis or proteolysis | Cystatin C | Lindholt et al. [18] | 2001 | Prospective study | Negative correlation with aneurysm size and expansion, no potential for predicting surgery | Aneurysm size and progression |
| Cathepsin S | Lv et al. [19] | 2012 | Prospective study | Positive correlation with aortic diameters, no correlation with AAA annual expansion rate | Aneurysm size and progression | |
| Circulating basement-membrane fragments | Ramazani et al. [20] | 2011 | Case control study | AAA patients had significantly increased levels of types IV and XVIII collagen compared with the controls | Aneurysm detection | |
| OPG | Koole et al. [23] | 2012 | Retrospective study | Aortic wall OPG was positively associated with established markers of AAA severity, while it appeared to be associated with lymphocytes and plasma cells | Aneurysm genesis and growth | |
| Tenascin-C (TN-C) |
Greenhalgh et al. [2] | 2010 | Follow-up study | TN-C is used to stratify risk in patients with AAA before intervention and also after endovascular repair | Aneurysm progression and treatment efficacy | |
|
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| Genomic biomarkers |
Telomere length | Wilson et al. [67] | 2008 | Case control study | Telomere: genomic DNA content being significantly reduced in wall biopsies of AAA compared to normal aortas | Aneurysm detection |
| AAA1 locus on chromosome 19q13 | Lillvis et al. [71] | 2011 | GWAS | CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and not in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and nonaneurysmal tissue samples | Aneurysm detection | |
| 9p21 | Thompson et al. [73] | 2009 | Cohort study | A significant association between rs10757278-G and the presence of AAA was found (P = 0.030). rs10757278 was not significantly associated with altered AAA growth rate | Aneurysm detection | |
| Wei et al. [74] | 2014 | Case control study | SNP rs10757278 and rs1333049 of chromosome 9p21-3 region were significantly associated with increased risk of AAA. This study revealed no association between polymorphisms and aortic diameters in AAA patients | Aneurysm genesis | ||
| CCRs | Katrancioglu et al. [75] | 2011 | Case control study | CCR2 heterozygote V64I polymorphism and allele frequency were more frequently observed in the AAA group | Aneurysm detection | |
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| Metabolomics | Lps | Takagi et al. [57] | 2009 | Meta-analysis | Lp(a) concentrations may be higher in patients with AAA than those in subjects without AAA | Aneurysm detection |
| Takagi et al. [60] | 2010 | Meta-analysis | Lower serum HDL cholesterol and higher serum LDL cholesterol may be associated with AAA presence | Aneurysm detection | ||
| Chan et al. [59] | 2013 | Case control study | Lipoprotein receptor-related protein 1 (LRP1) expression was found significantly lower in AAA patients than controls, while no significant correlation was shown between LRP1 expression and the size of AAA (P > 0.05) | Aneurysm detection | ||
| Giusti et al. [62] | 2009 | Case control study | Association between decreased expression levels of LRP5 gene in AAA patients | Aneurysm detection | ||
| Galora et al. [63] | 2013 | Case control study | LRP5 gene polymorphisms rs4988300 and rs3781590 were found independent genetic markers of AAA. AAA patients had significantly higher Lp(a) levels than control subjects (P < 0.0001) | Aneurysm detection | ||
| Vitamin D binding protein | Gamberi et al. [54] | 2011 | Proteomics | Negative correlation between DBP and AAA presence | Aneurysm detection | |
| Wong et al. [55] | 2013 | Randomized clinical study | An inverse relationship between vitamin D status and the presence of larger AAA was found, along with an inverse dose-response association between 25(OH)D concentrations and the size of AAA | Aneurysm size | ||
| Homocysteine | Wong et al. [56] | 2013 | Cross-sectional study | Plasma total homocysteine (tHcy) was found to be associated with the presence of AAA, while there was also a positive dose-response relationship between tHcy and abdominal aortic diameter | Aneurysm detection and size | |
| Phospholipases | Wallinder et al. [64] | 2012 | Case control study | Small AAA had increased levels of the enzyme glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) compared with the controls without aneurysm | Aneurysm size and detection | |
| Iron | Martinez-Pinna et al. [66] |
2014 | Local iron retention and altered iron recycling associated with high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated with AAA presence and clinical outcome | Aneurysm detection and progression | ||
MMPs: matrix-degrading metalloproteinases; tPA: tissue-like plasminogen activator; TNF-alpha: tumor necrosis factor-alpha; IL-6: interleukin-6; CRP: C reactive protein; hs: highly sensitive; Se: selenium; Lp(a): lipoprotein(a); a1-AT: alpha 1 antitrypsin; NGAL: neutrophil gelatinase-associated lipocalin; CCRs: chemokine receptors.