Unravelling the proteome of degenerative human mitral valves

Area of Science:

• Cardiovascular Biology
• Proteomics
• Molecular Medicine

Background:

• Degenerative mitral valve disease (DMVD), including mitral valve prolapse (MVP), is a prevalent valvular condition.
• MVP can lead to mitral regurgitation and adverse cardiovascular outcomes.
• The molecular mechanisms underlying human MVP pathogenesis remain largely uncharacterized.

Purpose of the Study:

• To perform the first large-scale proteome profiling of human mitral valve tissue from patients with MVP.
• To identify proteins and molecular events involved in MVP pathogenesis.
• To explore potential roles of identified proteins in cardiac remodeling associated with mitral regurgitation.

Main Methods:

• Proteome profiling of mitral valve tissue resected from patients with MVP.
• Identification of 1134 proteins.
• Validation of selected proteins using SWATH-MS and western blotting.
• Gene Ontology (GO) annotation for functional classification.

Main Results:

• A comprehensive proteome database of 1134 identified proteins was generated.
• GO annotation confirmed the relevance of these proteins in cardiovascular processes.
• Several structural and extracellular matrix proteins, including asporin, biglycan, decorin, lumican, mimecan, prolargin, versican, and vinculin, were identified with putative roles in MVP pathophysiology.

Conclusions:

• This study provides the first large-scale proteomic insights into human MVP.
• Identified proteins, particularly those in the extracellular matrix, are implicated in MVP pathogenesis.
• These findings offer potential targets for understanding and treating MVP and associated cardiac remodeling.