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Unravelling the proteome of degenerative human mitral valves
Authors:Hwee Tong Tan  Teck Kwang Lim  Arthur Mark Richards  Theodoros Kofidis  Kristine Leok‐Kheng Teoh  Lieng H Ling  Maxey C M Chung
Institution:1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;2. Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore;3. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;4. Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre, Singapore;5. Cardiac Department, National University Heart Centre, Singapore
Abstract:Degenerative mitral valve disease (DMVD), which includes the syndromes of mitral valve prolapse (MVP) and flail leaflet, is a common valvular condition which can be complicated by mitral regurgitation and adverse cardiovascular outcomes. Although several genetic and other studies of MVP in dog models have provided some information regarding the underlying disease mechanisms, the proteins and molecular events mediating human MVP pathogenesis have not been unraveled. In this study, we report the first large‐scale proteome profiling of mitral valve tissue resected from patients with MVP. A total of 1134 proteins were identified, some of which were validated using SWATH‐MS and western blotting. GO annotation of these proteins confirmed the validity of this proteome database in various cardiovascular processes. Among the list of proteins, we found several structural and extracellular matrix proteins, such as asporin, biglycan, decorin, lumican, mimecan, prolargin, versican, and vinculin, that have putative roles in the pathophysiology of MVP. These proteins could also be involved in the cardiac remodeling associated with mitral regurgitation. All MS data have been deposited in the ProteomeXchange with identifier PXD000774 ( http://proteomecentral.proteomexchange.org/dataset/PXD000774 ).
Keywords:Cell biology  Extracellular matrix  Mitral valve  Proteome profiling  SWATH‐MS
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