Abstract 261: Proteomic Analysis of Infrarenal and Suprarenal Aorta in a Kawasaki Disease Vasculitis Murine Model Associated with Infrarenal Abdominal Aorta Dilatation and Aneurysms

Abstract

Background: Kawasaki Disease (KD) is a childhood vasculitis that leads to coronary artery aneurysms and is the leading cause of acquired heart diseases among children in the USA. We have reported that the L actobacillus casei - c ell w all e xtract (LCWE)-induced murine model of KD vasculitis and coronary arteritis also induces abdominal aorta dilatation and aneurysms (AAA) that involve exclusively the infrarenal (IR) region of the abdominal aorta (AA) without affecting the suprarenal (SR)-AA. AAA predisposes tissue to dissection and rupture, and is potentially life-threatening in humans. While differences in blood flow, tissue elasticity and different embryonic origin of vascular cells have been proposed among possible explanations for the preferential location of AAA disease in the IR aorta, the mechanism(s) for this is still not known. Objective: To determine and compare the proteomes of the IR vs SR aorta regions in naïve mice and during KD vasculitis induced AAA development. Methods and Results: By using data-independent mass-spectrometry, we compared the proteomes of the IR and SR aortas isolated from control naïve mice and LCWE-injected KD vasculitis mice. Proteomic analysis revealed significant differential expression of 340 proteins between the IR aorta from control vs KD mice, and 407 differentially expressed proteins between the IR and SR aorta regions of KD mice. The differentially expressed proteins include those involved in cytoskeletal reorganization, cell motility and adhesion as well as acute phase and oxidative stress responses. Ingenuity Pathway Analysis reveals the activation of key regulators of innate immune responses as well as the ER Stress response. TGF-β1, IL-6, and IL-1β are regulators of several protein that were activated in the IR aortic tissues. Conclusion: Proteomic differences exist between normal AA vs AAA and in IR vs SR aorta regions isolated from mice developing AAA. We show that a broad inflammatory response is generated in the aneurysm which maybe critical for the development and progression of the AAA and may provide possible novel therapeutic targets. (Supported by AHA 17SDG33671141 to MNR and NIH R01AI07272607 to MA).