Moris et al. discuss several emerging biomarkers implicated in the pathophysiology of abdominal aortic aneurysms (AAAs) [1]. These include biomarkers related to AAA extracellular matrix homeostasis or proteolysis, cellular or signalling pathways, proteins released by intraluminal thrombi, circulating cells and inflammation, metabolomics and genetic biomarkers. One emerging biomarker which probably also deserves to be mentioned is 18F-fluorodeoxyglucose (18F-FDG).
18F-FDG uptake detected by positron emission tomography (PET) is used to assess hypermetabolic activity of cells in tumors and inflammatory processes [2, 3]. Inflammation plays a key role in the development of AAAs [4]. AAA regions displaying increased 18F-FDG uptake show increased inflammatory activity and are enriched in leukocytes [5]. Increased 18F-FDG uptake in AAAs is associated with inflammation, aortic wall instability, and rupture risk [6]. Therefore, 18F-FDG uptake might be a new technique to study AAA disease in vivo and may improve prediction of AAA rupture risk [6, 7]. The prognostic value of 18F-FDG uptake was verified by a study reporting increased focal uptake of 18F-FDG in patients with large, rapidly expanding, or symptomatic AAAs that are prone to rupture [8].
In a recent study [9], biopsies of the AAA wall were obtained from regions with no 18F-FDG uptake and from regions positive for 18F-FDG uptake, both at the site positive for uptake and at a distant negative site of the AAA wall. The sites with a positive 18F-FDG uptake were characterized by a higher number of adventitial inflammatory cells and by a reduction of smooth muscle cells in the media compared with the negative 18F-FDG samples [9]. It was concluded that positive 18F-FDG uptake in the AAA wall is associated with an active inflammatory process and alterations of the expression of genes involved in the remodelling of adventitia and collagen degradation, which potentially participate in the weakening of the AAA wall preceding rupture [9]. Another use of 18F-FDG may be in endovascular AAA repair (EVAR) procedures [10]. Increased 18F-FDG uptake following EVAR may be an indirect predictor of AAA sac enlargement due to the presence of an endoleak (even if this is not detected by imaging modalities) and increased AAA rupture risk [10].
18F-FDG uptake may be a more promising biomarker for AAAs than some of those discussed by the authors (e.g., cystatin C and neutrophil gelatinase-associated lipocalin [NGAL]) [1]. There is evidence that NGAL and cystatin C are affected by kidney function, as well as by statins [11–13]. In turn, patients with AAAs may have impaired kidney function and may well be on statins [14]. To make things even more complicated, statins can improve renal function in vascular patients [15]. These factors make the use of these markers subject to confounding.
In conclusion, 18F-FDG may prove to be a useful biomarker in the pathogenesis of AAAs. Future studies should investigate these possibilities.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
References
- 1.Moris D, Mantonakis E, Avgerinos E. Novel biomarkers of abdominal aortic aneurysm disease: identifying gaps and dispelling misperceptions. BioMed Research International. 2014;2014:13 pages. doi: 10.1155/2014/925840.925840 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Miyagawa M, Yokoyama R, Nishiyama Y, Ogimoto A, Higaki J, Mochizuki T. Positron emission tomography-computed tomography for imaging of inflammatory cardiovascular diseases. Circulation Journal. 2014;78(6):1302–1310. doi: 10.1253/circj.cj-14-0250. [DOI] [PubMed] [Google Scholar]
- 3.Tantiwongkosi B, Yu F, Kanard A, Miller FR. Role of (18)F-FDG PET/CT in pre and post treatment evaluation in head and neck carcinoma. World Journal of Radiology. 2014;6(5):177–191. doi: 10.4329/wjr.v6.i5.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Paraskevas KI, Andrikopoulou M, Anastasakis E, Perrea D, Mikhailidis DP. Oxidative stress in the pathogenesis of abdominal aortic aneurysms: a possible pathway for the effect of statins? Angiology. 2010;61(2):226–227. doi: 10.1177/0003319709353168. [DOI] [PubMed] [Google Scholar]
- 5.Defawe OD, Hustinx R, Defraigne JO, Limet R, Sakalihasan N. Distribution of F-18 fluorodeoxyglucose (F-18 FDG) in abdominal aortic aneurysm: high accumulation in macrophages seen on PET imaging and immunohistology. Clinical Nuclear Medicine. 2005;30(5):340–341. doi: 10.1097/01.rlu.0000159681.24833.95. [DOI] [PubMed] [Google Scholar]
- 6.Reeps C, Essler M, Pelisek J, Seidl S, Eckstein H-H, Krause B-J. Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms. Journal of Vascular Surgery. 2008;48(2):417–423. doi: 10.1016/j.jvs.2008.03.059. [DOI] [PubMed] [Google Scholar]
- 7.Paraskevas KI, Tzovaras AA, Gentimi F, Kyriakides ZS, Mikhailidis DP. Predictors of abdominal aortic aneurysm (AAA) growth and AAA rupture risk besides AAA Size: fact or fiction? Angiology. 2010;61(4):321–323. doi: 10.1177/0003319709360526. [DOI] [PubMed] [Google Scholar]
- 8.Sakalihasan N, Van Damme H, Gomez P, et al. Positron emission tomography (PET) evaluation of abdominal aortic aneurysm (AAA) European Journal of Vascular and Endovascular Surgery. 2002;23(5):431–436. doi: 10.1053/ejvs.2002.1646. [DOI] [PubMed] [Google Scholar]
- 9.Courtois A, Nusgens BV, Hustinx R, et al. 18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture. Journal of Nuclear Medicine. 2013;54(10):1740–1747. doi: 10.2967/jnumed.112.115873. [DOI] [PubMed] [Google Scholar]
- 10.Paraskevas KI, Tzovaras AA, Stathopoulos V, Gentimi F, Mikhailidis DP. Increased fluorodeoxyglucose uptake following endovascular abdominal aortic aneurysm repair: a predictor of endoleak? The Open Cardiovascular Medicine Journal. 2010;4:117–119. doi: 10.2174/1874192401004010117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Alharazy SM, Kong N, Saidin R, et al. Serum neutrophil gelatinase-associated lipocalin and cystatin C are early biomarkers of contrast-induced nephropathy after coronary angiography in patients with chronic kidney disease. Angiology. 2014;65(5):436–442. doi: 10.1177/0003319713483918. [DOI] [PubMed] [Google Scholar]
- 12.Fassett RG, Robertson IK, Ball MJ, Geraghty DP, Cardinal JW, Coombes JS. Effects of atorvastatin on NGAL and cystatin C in chronic kidney disease: a post hoc analysis of the LORD trial. Nephrology Dialysis Transplantation. 2012;27(1):182–189. doi: 10.1093/ndt/gfr193. [DOI] [PubMed] [Google Scholar]
- 13.Alharazy SM, Kong N, Saidin R, et al. Neutrophil gelatinase-associated lipocalin as an early marker of contrast-induced nephropathy after coronary angiography. Angiology. 2014;65(3):216–223. doi: 10.1177/0003319712474947. [DOI] [PubMed] [Google Scholar]
- 14.Paraskevas KI, Wierzbicki AS, Mikhailidis DP. Statins and noncardiac vascular disease. Current Opinion in Cardiology. 2012;27(4):392–397. doi: 10.1097/HCO.0b013e328353add9. [DOI] [PubMed] [Google Scholar]
- 15.Alnaeb ME, Youssef F, Mikhailidis DP, Hamilton G. Short-term lipid-lowering treatment with atorvastatin improves renal function but not renal blood flow indices in patients with peripheral arterial disease. Angiology. 2006;57(1):65–71. doi: 10.1177/000331970605700109. [DOI] [PubMed] [Google Scholar]