Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans

<p><strong>Objective:</strong><br /> Discovery of novel biomarkers for abdominal aortic aneurysm growth (AAA) prediction.</p><br /> <p><strong>Background:</strong><br /> Novel biomarker of AAA growth is a recognised priority in research. O...

Celý popis

Podrobná bibliografie
Hlavní autoři: Lee, R, Cassimee, I, Huang, H, Lapolla, P, Ngetich, E, Chandrashekar, A, Charles, P, Kessler, B, Fischer, R, Handa, A
Médium: Journal article
Jazyk:English
Vydáno: Lippincott, Williams & Wilkins 2020
Popis
Shrnutí:<p><strong>Objective:</strong><br /> Discovery of novel biomarkers for abdominal aortic aneurysm growth (AAA) prediction.</p><br /> <p><strong>Background:</strong><br /> 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.</p><br /> <p><strong>Methods:</strong><br /> 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.</p><br /> <p><strong>Results:</strong><br /> 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.</p><br /> <p><strong>Conclusion:</strong><br /> 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.</p>