Poster Session 1 - C1
1Da Hye Kim, 1,2Uros Kuzmanov, 1,3Hadipour-Lakmehsari, 4,5Gavin Y. Oudit, 1,3Anthony O. Gramolini
1 Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2 Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada; 3 Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada; 4 Department of Medicine, University of Alberta, Edmonton, AB, Canada; 5 Mazankowski Alberta Heart Institute, Edmonton, AB, Canada
Ischemic cardiomyopathy (ICM) is the most common cause of heart failure. Despite its high incidence and prevalence, current therapeutic strategies remain limited and ICM patients ultimately progress towards HF. The coordination of multiple signaling pathways is understood to be involved in this deterioration of cardiac function, but we have yet to fully elucidate the molecular events underlying ICM. We have previously enriched for and studied phosphoproteomics of a phospholamban (PLN) R9C mouse model of dilated cardiomyopathy (DCM) to identify a novel association between Notch-1 signaling and DCM. Here, we extend this work to develop a novel methodology using LC-MS/MS (liquid chromatography-tandem mass spectrometry) to identify differentially regulated signaling pathways that underlie the progression of ICM using patient samples. Human ventricular tissue samples (ICM vs. non-failing hearts, n = 5) will be labeled with tandem mass tags for relative quantification and subjected to LC-MS/MS for global proteomic analysis. The same samples will be further enriched for phosphorylated, acetylated, and succinylated peptides before proceeding to LC-MS/MS. With the integration of global proteomics and post-translationally modification analysis, pathway enrichment analysis will identify perturbed signaling networks in human ICM samples of left ventricle (LV) infarct, LV peri-infarct, LV non-infarct regions, and right ventricle using non-failing human hearts as a control condition. This will be the first large-scale integrative study using human ICM tissue, advancing our understanding of signaling mechanisms involved in ICM and providing us with novel therapeutic targets.