Mitral valve prolapse is associated with altered extracellular matrix gene expression patterns

• A transcriptome analysis was performed to study alterations in ECM gene expression in human MVP.
• Changes in proteolytic gene expression, including MMPs, cathepsins, and ADAMTSs occur in MVP.
• Genes involved in the TGF-beta signaling pathway are enriched in human MVP.

Mitral valve prolapse (MVP) is the leading indication for isolated mitral valve surgery in the United States. Disorganization of collagens and glycosaminoglycans in the valvular extracellular matrix (ECM) are histological hallmarks of MVP. We performed a transcriptome analysis to study the alterations in ECM-related gene expression in humans with sporadic MVP. Mitral valve specimens were obtained from individuals undergoing valve repair for MVP (n = 7 patients) and from non-beating heart-tissue donors (n = 3 controls). Purified RNA was subjected to whole-transcriptome microarray analysis. Microarray results were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Gene ontology enrichment analysis was performed. 2046 unique genes showed significant differential expression (false discovery rate < 0.5%). After demonstrating appropriate sample clustering, microarray results were globally validated using a subset of 22 differentially expressed genes by RT-qPCR (Pearson's correlation r = 0.65, p = 0.001). Gene ontology enrichment analyses performed with ErmineJ and DAVID Bioinformatics Database demonstrated overrepresentation of ECM components (p < 0.05). Functional annotation clustering calculated enrichment of ECM-related ontology groups (enrichment score = 4.1). ECM-related gene expression is significantly altered in MVP. Our study is consistent with the histologically observed alterations in collagen and mucopolysaccharide profiles of myxomatous mitral valves. Furthermore, whole-transcriptome analyses suggest dysregulation of multiple pathways, including TGF-beta signaling.