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...
| Автори: | , , , , , , , , , |
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| Формат: | Journal article |
| Мова: | English |
| Опубліковано: |
Lippincott, Williams & Wilkins
2020
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| _version_ | 1826308622239399936 |
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| author | Lee, R Cassimee, I Huang, H Lapolla, P Ngetich, E Chandrashekar, A Charles, P Kessler, B Fischer, R Handa, A |
| author_facet | Lee, R Cassimee, I Huang, H Lapolla, P Ngetich, E Chandrashekar, A Charles, P Kessler, B Fischer, R Handa, A |
| author_sort | Lee, R |
| collection | OXFORD |
| description | <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> |
| first_indexed | 2024-03-07T07:22:03Z |
| format | Journal article |
| id | oxford-uuid:f2344f99-d5a7-493f-a387-71dd350b9a5b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:22:03Z |
| publishDate | 2020 |
| publisher | Lippincott, Williams & Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:f2344f99-d5a7-493f-a387-71dd350b9a5b2022-10-18T14:29:12ZIntegrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humansJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f2344f99-d5a7-493f-a387-71dd350b9a5bEnglishSymplectic ElementsLippincott, Williams & Wilkins2020Lee, RCassimee, IHuang, HLapolla, PNgetich, EChandrashekar, ACharles, PKessler, BFischer, RHanda, A<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> |
| spellingShingle | Lee, R Cassimee, I Huang, H Lapolla, P Ngetich, E Chandrashekar, A Charles, P Kessler, B Fischer, R Handa, A Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
| title | Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
| title_full | Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
| title_fullStr | Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
| title_full_unstemmed | Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
| title_short | Integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
| title_sort | integrated plasma and tissue proteomics reveals attractin release by intraluminal thrombus of abdominal aortic aneurysms and improves aneurysm growth prediction in humans |
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