Phosphoproteomic analysis of cardiac biowires, cardiac hypertrophy patient explants, and hypertrophic mouse heart

we apply and evaluate an integrative mass spectrometry-based tissue profiling strategy that allows for a global quantitative phospho-proteomic survey of normal and disease tissue from human, mouse and OOC-derived specimens. The applicability and utility of this approach was tested in the context of fibrotic cardiac tissue samples from Biowire OOC specimens versus cardiac tissue surgical explants from hypertrophic patients and a transaortic constriction mouse pressure-overload model. Unique attributes and phosphorylation signatures specific to each tissue source were identified, but the results clearly showed that clinically-actionable biological inferences are generated by leveraging commonalities exhibited across the compendium. To validate the application of the cross-platform analytical framework, proof of principle drug testing was performed for selection of anti-fibrotic compounds targeting one of the identified fibrosis-related kinases, GSK3, consistent with a role as a key mediator of fibrosis.