P106. Distinct Biochemical Profile in Human Thoracic Aneurysms with Associated Valve Dysfunction: Integrative Phosphoproteomic Analysis from the MultiTAAD Multiomic Database
Presented During: POD Abstracts (Available for viewing in the exhibit hall for the duration of the meeting)
University of Toronto
Toronto, ON
Canada - Contact Me
Dr. Elbatarny is a 3rd year Cardiac Surgery Resident at the University of Toronto and PhD candidate in the Department of Physiology. Previously, she completed her BSc (Life Sciences, 2015) and MD (2019) at Queen's University. Currently, she is part of the Surgeon-Scientist Training and Clinician Investigator Programs and is pursuing PhD studies in Multi-omic Bioinformatics of Hereditary Aortopathy. Dr. Elbatarny's interest in overcoming barriers to accessing cardiac surgical care also led her to participate in global cardiac surgical rotations and establish ongoing international collaborations. She has furthermore applied previous experience from entrepreneurship projects, marketing, and graphic design to produce surgical patient education videos, participate in health awareness campaign development, and medical illustration.
Thursday, April 25, 2024: 5:38 PM - 7:00 PM
Sheraton Times Square
Room: Central Park
Description
Objective: Thoracic aortopathy (TAAD) often occurs with aortic valve pathology (stenosis, AS or regurgitation, AR) which may impact TAAD phenotype and severity. We compared proteomic and phosphoproteomic profiles of TAAD aortas with AS, AR, mixed (AS+AR), and normal valves to determine whether valve disease-associated aortopathy is phenotypically distinct.
Methods: 176 aortic samples (root, ascending, and arch) were collected prospectively from TAAD and dissection individuals with various aortic valve phenotypes (Figure 1A). All samples were analyzed using a novel deep-coverage protocol for mass spectrometry proteomics (data independent acquisition) and double enrichment technique to identify phosphorylation sites in detected proteins. Proteomic and phosphoproteomic data were directly compared by valve morphology (p<0.05 considered significant) to determine impact of valve function on aortopathy biochemical profile.
Results: Samples included N=123 males (74%) and mean age was 58±16. Among samples derived from individuals with concomitant valve disease, N=70 were AR-associated, N=41 were AS-associated, and N=11 were AS+AR. Considering the entire cohort, we quantified 6094 proteins and 2125 phosphorylation sites. At the proteomic level, when AS+AR was compared to normal valve-associated aortopathy, 721 proteins were differentially expressed (174 up in AS+AR, 547 down in AS+AR Figure 1B). Additionally, AR-associated aortopathy was associated with substantial phenotypic differences in both proteomic (total proteins 651; up in AR: 216; down in AR: 435) and phosphoproteomic data sets (total sites 210; hyperphosphorylated in AR: 96; hypophosphorylated in AR: 114 Figure 1B). Examining proteomic profiles in more detail, cytoskeletal proteins were predominantly decreased in AR-associated aortopathy while both hyper- and hypo-phosphorylation of cytoskeletal proteins was observed in AR (Figure 1C).
Conclusion: We performed the first multiproteomic analysis of aortopathy by aortic valve function on a large cohort of human samples using a novel protocol. Valve dysfunction, especially AR, is associated with altered aortic tissue biochemistry which suggests differences in mechanism and progression of aortopathy.
Authors
Malak Elbatarny (1), Uros Kuzmanov (2), Daniella Eliathamby (3), Jennifer Chung (4), Craig Simmons (5), Anthony Gramolini (2), Maral Ouzounian (3)
Institutions
(1) TGH / St Michael's, Toronto, ON, (2) University of Toronto, Toronto, NA, (3) Toronto General Hospital, Toronto, ON, (4) Toronto General Hospital, Toronto, Ontario, (5) University of Toronto, Toronto, Ontario
Methods: 176 aortic samples (root, ascending, and arch) were collected prospectively from TAAD and dissection individuals with various aortic valve phenotypes (Figure 1A). All samples were analyzed using a novel deep-coverage protocol for mass spectrometry proteomics (data independent acquisition) and double enrichment technique to identify phosphorylation sites in detected proteins. Proteomic and phosphoproteomic data were directly compared by valve morphology (p<0.05 considered significant) to determine impact of valve function on aortopathy biochemical profile.
Results: Samples included N=123 males (74%) and mean age was 58±16. Among samples derived from individuals with concomitant valve disease, N=70 were AR-associated, N=41 were AS-associated, and N=11 were AS+AR. Considering the entire cohort, we quantified 6094 proteins and 2125 phosphorylation sites. At the proteomic level, when AS+AR was compared to normal valve-associated aortopathy, 721 proteins were differentially expressed (174 up in AS+AR, 547 down in AS+AR Figure 1B). Additionally, AR-associated aortopathy was associated with substantial phenotypic differences in both proteomic (total proteins 651; up in AR: 216; down in AR: 435) and phosphoproteomic data sets (total sites 210; hyperphosphorylated in AR: 96; hypophosphorylated in AR: 114 Figure 1B). Examining proteomic profiles in more detail, cytoskeletal proteins were predominantly decreased in AR-associated aortopathy while both hyper- and hypo-phosphorylation of cytoskeletal proteins was observed in AR (Figure 1C).
Conclusion: We performed the first multiproteomic analysis of aortopathy by aortic valve function on a large cohort of human samples using a novel protocol. Valve dysfunction, especially AR, is associated with altered aortic tissue biochemistry which suggests differences in mechanism and progression of aortopathy.
Authors
Malak Elbatarny (1), Uros Kuzmanov (2), Daniella Eliathamby (3), Jennifer Chung (4), Craig Simmons (5), Anthony Gramolini (2), Maral Ouzounian (3)
Institutions
(1) TGH / St Michael's, Toronto, ON, (2) University of Toronto, Toronto, NA, (3) Toronto General Hospital, Toronto, ON, (4) Toronto General Hospital, Toronto, Ontario, (5) University of Toronto, Toronto, Ontario
Presentation Duration
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