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Mitral valve prolapse is associated with altered extracellular matrix gene expression patterns.
David G Greenhouse1, Alison Murphy1, Paolo Mignatti2
1Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York, NY, United States.
Gene
|April 12, 2016
Summary
Mitral valve prolapse (MVP) involves changes in the heart valve's extracellular matrix. This study found significant alterations in ECM-related gene expression in MVP patients, impacting collagen and TGF-beta signaling.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Mitral valve prolapse (MVP) is a primary reason for mitral valve surgery in the US.
- Histological hallmarks of MVP include disorganized collagens and glycosaminoglycans in the valvular extracellular matrix (ECM).
Purpose of the Study:
- To investigate alterations in ECM-related gene expression in human sporadic MVP using transcriptome analysis.
Main Methods:
- Whole-transcriptome microarray analysis of mitral valve tissue from MVP patients (n=7) and controls (n=3).
- Validation of microarray results using quantitative reverse transcription polymerase chain reaction (RT-qPCR).
- Gene ontology enrichment analysis using ErmineJ and DAVID Bioinformatics Database.
Main Results:
- 2046 unique genes exhibited significant differential expression (FDR <0.5%).
- RT-qPCR validation confirmed microarray findings (Pearson's r=0.65, p=0.001).
- Gene ontology analysis revealed significant overrepresentation of ECM components and enrichment of ECM-related pathways, including TGF-beta signaling.
Conclusions:
- ECM-related gene expression is significantly altered in MVP, aligning with known histological changes in myxomatous mitral valves.
- Whole-transcriptome analysis indicates dysregulation of multiple pathways, notably TGF-beta signaling, in MVP pathogenesis.
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