Unravelling the proteome of degenerative human mitral valves.
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).
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Hwee Tong
HT
Tan
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
Teck Kwang
TK
Lim
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Arthur Mark
AM
Richards
Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre, Singapore.
Theodoros
T
Kofidis
Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre, Singapore.
Kristine Leok-Kheng
KL
Teoh
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Cardiac Department, National University Heart Centre, Singapore.
Lieng H
LH
Ling
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
Maxey C M
MC
Chung
D058578:Biglycan / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D030562:Databases, Protein; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D007632:Keratan Sulfate / Q000378:metabolism; D000071234:Lumican; D008943:Mitral Valve / Q000378:metabolism* / Q000503:physiopathology; D008944:Mitral Valve Insufficiency / Q000378:metabolism* / Q000503:physiopathology; D008945:Mitral Valve Prolapse / Q000378:metabolism / Q000503:physiopathology; D058977:Molecular Sequence Annotation; D020543:Proteome / Q000032:analysis*; D053719:Tandem Mass Spectrometry; D053675:Versicans / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
C439889:ASPN protein, human; C546884:BGN protein, human; D058578:Biglycan; D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; C000604306:LUM protein, human; D000071234:Lumican; D020543:Proteome; C508322:VCAN protein, human; C488955:VCL protein, human; D016596:Vinculin; D053675:Versicans; D007632:Keratan Sulfate
Cell biology; Extracellular matrix; Mitral valve; Proteome profiling; SWATH-MS