Abstract 466: Metabolome Profile of Experimental Abdominal Aortic Abdominal Aneurysms
Abdominal aortic aneurysm (AAA) is a degenerative inflammatory disease involving multiple metabolic and signaling pathways. To date, no circulating biomarker accurately identifies AAAs in asymptomatic persons or predicts AAA progression or response to treatment following endovascular exclusion. This study sought to define the serum metabolome, the complete set of small molecule metabolites in experimental AAAs. Methods: AAAs were created via intra-aortic porcine pancreatic elastase (PPE) infusion in male C57BL/6J mice or 28-day subcutaneous infusion of angiotensin (Ang) II in male ApoE knockout (KO) mice. PBS was infused as the controls. Aortic diameter was measured via ultrasonography. Sera were prepared at sacrifice (14 (PPE) or 28 (Ang II) days following AAA initiation). Serum metabolites were identified via ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and analyzed via O2PLS method using SIMCA software. Results: Substantial aortic enlargement occurred in C57BL/6J and ApoE KO mice following PPE and Ang II infusion compared to PBS-infused mice. In UPLC-MS assays, both O2PLS 2D and 3D score plots identified distinct metaboloic signatures between non-aneurysmal C57BL/6J and ApoE KO mice (PBS infusion). Further, 3D score plot differentiated aneurysmal (PPE or Ang II infusion) from non-aneurysmal metabolome in both PPE and Ang II infusion models. However, the 2D score plot failed to demonstrate the difference in the later model. Conclusion: Experimental AAA generates a characteristic metabolome, potentially providing pathogenetic clues as well as a convenient and reproducible biomarker for monitoring disease progression.
Author Disclosures: X. Wang: None. R.L. Dalman: None. H. Xuan: None. N. Fujimura: None. H. Deng: None. Y. Iida: None. M.P. Snyder: None. B. Xu: None.
- © 2015 by American Heart Association, Inc.