Abstract 228: Multi-omics Mapping Generates a Molecular Atlas of the Aortic Valve and Reveals Networks Driving Disease

• DOI: 10.1161/atvb.38.suppl_1.228
• Publication Date: 2019-03-12T14:49:15Z
• Authors: Florian Schlotter; Arda Halu; Shinji Goto; Mark C Blaser; Simon C Body; Lang H Lee; Hideyuki Higashi; Daniel M DeLaughter; Joshua D Hutcheson; Payal Vyas; Tan H Pham; Maximillian A Rogers; Amitabh Sharma; Christine E Seidman; Joseph Loscalzo; Jonathan G Seidman; Masanori Aikawa; Sasha A Singh; Elena Aikawa
• Keywords: Proteome

Background: No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without replacement. The search therapeutics and early diagnostics is challenging since CAVD presents in multiple pathological stages. Methods: A total of 25 human stenotic valves obtained from replacement surgery were analyzed by modalities, including transcriptomics global unlabeled tandem-mass-tagged proteomics liquid chromatography-mass spectrometry. Results: Global transcriptional protein expression signatures differed between the non-diseased, fibrotic, stages CAVD, with consistent trends gene across Anatomical microlayers exhibited unique proteome profiles that maintained throughout progression, revealed GFAP as specific marker valvular interstitial cells (VICs) spongiosa layer. progression was marked an emergence smooth muscle cell activation, inflammation, calcification-related pathways. Proteins overrepresented disease-prone fibrosa are functionally annotated to fibrosis calcification pathways, we found that, vitro , fibrosa-derived VICs demonstrated greater potential than those ventricularis. These studies confirmed microlayer-specific preserved cultured VICs, exposed TNAP-dependent TNAP-independent calcifying stimuli had distinct profiles, both overlapped whole tissue. Network analysis protein-protein interaction networks significant closeness inflammatory fibrotic diseases. Conclusions: spatially- temporally-resolved multi-omics systems biology strategy identifies first molecular regulatory cardiac condition cure, describes endophenotype characterization broadly applicable comprehensive omics cardiovascular