Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

• Published in: Clinica chimica acta 2024-02, Vol.554, p.117786-117786, Article 117786
• Main Authors: Vanmaele, Alexander, Bouwens, Elke, Hoeks, Sanne E, Kindt, Alida, Lamont, Lieke, Fioole, Bram, Moelker, Adriaan, ten Raa, Sander, Hussain, Burhan, Oliveira-Pinto, José, Ijpma, Arne S, van Lier, Felix, Akkerhuis, K. Martijn, Majoor-Krakauer, Danielle F, Hankemeier, Thomas, de Rijke, Yolanda, Verhagen, Hence JM, Boersma, Eric, Kardys, Isabella
• Format: Article
• Language: English
• Subjects: Abdominal aortic aneurysm; Biomarkers; EVAR; Multi-omics; Volume
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2024.117786

•We performed proteomics and metabolomics in 108 AAA and 200 post-EVAR patients.•Circulating multi-omics identified several biomarkers and mechanisms in AAA patients.•Plasma concentrations of uPA and branched-chain amino acids correlated with AAA volume.•LDLR and the monoacylglycerols strongly associated with post-EVAR aneurysm sac size.•Post-EVAR aneurysm sac change was reflected by a distinct multi-omics signature. Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and −0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, −0.050 (-0.064, -0.037) per Z-score LDL-receptor, −0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and −0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.