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

Clinica Chimica Acta, 2024

Vanmaele A., Bouwens E., Hoeks S., Kindt A., Lamont L., Fioole B., Moelker A., ten Raa S., Hussain B., Oliveira-Pinto J., Ijpma A., van Lier F., Akkerhuis K., Majoor-Krakauer D., Hankemeier T., de Rijke Y., Verhagen H., Boersma E., Kardys I.

Disease areaApplication areaSample typeProducts
CVD
Patient Stratification
Plasma
Olink Target 96

Olink Target 96

Abstract

Background and aims
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.

Materials and methods
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.

Results
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.

Conclusions
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.

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