title: Differential MicroRNA Expression Profile in Myxomatous Mitral Valve Prolapse and Fibroelastic Deficiency Valves.
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.
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228, Singapore. mdccyt@nus.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. mdccyt@nus.edu.sg.
authors.forename: Yei-Tsung
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228, Singapore. mdcwaju@nus.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. mdcwaju@nus.edu.sg.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228, Singapore. abbiwsy@hotmail.com.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. abbiwsy@hotmail.com.
authors.forename: Abby S Y
authors.initials: AS
authors.lastname: Wee
authors.affiliation: Department of Cardiology, Tan Tock Seng Hospital, Singapore 308433, Singapore. quek_wei_yong@ttsh.com.sg.
authors.forename: Quek-Wei
authors.initials: QW
authors.lastname: Yong
authors.affiliation: Department of Cardiology, National University Heart Centre, Singapore 119228, Singapore. edgar_tay@nuhs.edu.sg.
authors.forename: Edgar Lik-Wui
authors.initials: EL
authors.lastname: Tay
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. surwoocc@nus.edu.sg.
authors.forename: Chin Cheng
authors.initials: CC
authors.lastname: Woo
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. vitaly_sorokin@nuhs.edu.sg.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Sorokin
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228, Singapore. arthur_mark_richards@nuhs.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. arthur_mark_richards@nuhs.edu.sg.|Department of Cardiology, National University Heart Centre, Singapore 119228, Singapore. arthur_mark_richards@nuhs.edu.sg.|Christchurch Heart Institute, University of Otago, Christchurch 8014, New Zealand. arthur_mark_richards@nuhs.edu.sg.
authors.forename: Arthur Mark
authors.initials: AM
authors.lastname: Richards
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228, Singapore. lieng_hsi_ling@nuhs.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. lieng_hsi_ling@nuhs.edu.sg.|Department of Cardiology, National University Heart Centre, Singapore 119228, Singapore. lieng_hsi_ling@nuhs.edu.sg.
authors.forename: Lieng-Hsi
authors.initials: LH
authors.lastname: Ling
mesh_terms: D020413:3' Untranslated Regions; D003198:Computer Simulation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008943:Mitral Valve / Q000473:pathology*; D008945:Mitral Valve Prolapse / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
keywords: degererative mitral valve disease (DMVD); fibroelastic deficiency (FED); microRNA; myxomatous mitral valve prolapse (MMVP)