Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans.
Lee R., Cassimee I., Huang H., Lapolla P., Ngetich E., Chandrashekar A., Charles P., Kessler B., Fischer R., Handa A.
OBJECTIVE: Discovery of novel biomarkers for abdominal aortic aneurysm growth (AAA) prediction. BACKGROUND: Novel biomarker of AAA growth is a recognised priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction. METHODS: Patients were prospectively recruited. Plasma samples were collected at baseline (n = 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n = 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10-12 weeks after surgery (n = 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n = 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry (LC-MS/MS) workflow to discover novel biomarkers. RESULTS: We discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the AUROC for predicting no growth and fast growth of AAA at 12 months is 85% and 76%, respectively. CONCLUSION: We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.