title: Integrated microRNA and messenger RNA analysis in aortic stenosis.
abstract: Aortic valve stenosis (AS) is a major cause of morbidity and mortality, with no effective medical therapies. Investigation into the underlying biology of AS in humans is limited by difficulties in obtaining healthy valvular tissue for use as a control group. However, micro-ribonucleic acids (miRNAs) are stable in post-mortem tissue. We compared valve specimens from patients undergoing aortic valve replacement for AS to non-diseased cadaveric valves. We found 106 differentially expressed miRNAs (p < 0.05, adjusted for multiple comparisons) on microarray analysis, with highly correlated expression among up- and down-regulated miRNAs. Integrated miRNA/gene expression analysis validated the microarray results as a whole, while quantitative polymerase chain reaction confirmed downregulation of miR-122-5p, miR-625-5p, miR-30e-5p and upregulation of miR-21-5p and miR-221-3p. Pathway analysis of the integrated miRNA/mRNA network identified pathways predominantly involved in extracellular matrix function. A number of currently available therapies target products of upregulated genes in the integrated miRNA/mRNA network, with these genes being predominantly more peripheral members of the network. The identification of a group of tissue miRNA associated with AS may contribute to the development of new therapeutic approaches to AS. This study highlights the importance of systems biology-based approaches to complex diseases.
authors.affiliation: Kolling Institute, University of Sydney, Australia.|Department of Cardiology, Royal North Shore Hospital, Sydney, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Coffey
authors.affiliation: Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Michael J A
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: L Vicky
authors.initials: LV
authors.lastname: Phillips
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Ivor F
authors.initials: IF
authors.lastname: Galvin
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Bunton
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Jones
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger