Abstract
Myxomatous mitral valve prolapse (MMVP) and fibroelastic deficiency (FED) are two common variants of degenerative mitral valve disease (DMVD), which is a leading cause of mitral regurgitation worldwide. While pathohistological studies have revealed differences in extracellular matrix content in MMVP and FED, the molecular mechanisms underlying these two disease entities remain to be elucidated. By using surgically removed valvular specimens from MMVP and FED patients that were categorized on the basis of echocardiographic, clinical and operative findings, a cluster of microRNAs that expressed differentially were identified. The expressions of has-miR-500, -3174, -17, -1193, -646, -1273e, -4298, -203, -505, and -939 showed significant differences between MMVP and FED after applying Bonferroni correction (p < 0.002174). The possible involvement of microRNAs in the pathogenesis of DMVD were further suggested by the presences of in silico predicted target sites on a number of genes reported to be involved in extracellular matrix homeostasis and marker genes for cellular composition of mitral valves, including decorin (DCN), aggrecan (ACAN), fibromodulin (FMOD), α actin 2 (ACTA2), extracellular matrix protein 2 (ECM2), desmin (DES), endothelial cell specific molecule 1 (ESM1), and platelet/ endothelial cell adhesion molecule 1 (PECAM1), as well as inverse correlations of selected microRNA and mRNA expression in MMVP and FED groups. Our results provide evidence that distinct molecular mechanisms underlie MMVP and FED. Moreover, the microRNAs identified may be targets for the future development of diagnostic biomarkers and therapeutics.
Highlights
Valvular heart disease (VHD) is an important public health concern with an age-dependent prevalence [1,2]
degenerative mitral valve disease (DMVD) can be classified into two subtypes on the basis of clinical patterns, imaging findings and gross surgical appearances: (1) billowing mitral valve (alternatively known as Barlow’s disease or myxomatous mitral valve prolapse (MMVP)), characterized by excessive, diffuse accumulation of glycosaminoglycan material; and (2) fibroelastic deficiency (FED) which is believed to be caused by disturbances in the homeostasis of connective tissue production [3,4,5,6,7]
Echocardiography was used to determine DMVD type (MMVP or FED), and human mitral valve tissues obtained during corrective surgery were subjected for gene expression analysis
Summary
Valvular heart disease (VHD) is an important public health concern with an age-dependent prevalence [1,2]. DMVD can be classified into two subtypes on the basis of clinical patterns, imaging findings and gross surgical appearances: (1) billowing mitral valve (alternatively known as Barlow’s disease or myxomatous mitral valve prolapse (MMVP)), characterized by excessive, diffuse accumulation of glycosaminoglycan material; and (2) fibroelastic deficiency (FED) which is believed to be caused by disturbances in the homeostasis of connective tissue production [3,4,5,6,7]. Echocardiography was used to determine DMVD type (MMVP or FED), and human mitral valve tissues obtained during corrective surgery were subjected for gene expression analysis. Using qPCR methods, web-based microRNA target and pathway predictive algorithms, the expressions of a cluster of microRNAs and predicted target genes that were reported to be dysregulated in diseased mitral valves and contributed to the progression of myxomatous accumulation were compared between MMVP and FED cohorts
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