作者: Sean Coffey , Michael JA Williams , L Vicky Phillips , Ivor F Galvin , Richard W Bunton
DOI: 10.1038/SREP36904
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摘要: Aortic valve stenosis (AS) is a major cause of morbidity and mortality, with no effective medical therapies. Investigation into the underlying biology AS in humans limited by difficulties obtaining healthy valvular tissue for use as control group. However, micro-ribonucleic acids (miRNAs) are stable post-mortem tissue. We compared specimens from patients undergoing aortic replacement to non-diseased cadaveric valves. found 106 differentially expressed miRNAs (p < 0.05, adjusted multiple comparisons) on microarray analysis, highly correlated expression among up- down-regulated miRNAs. Integrated miRNA/gene analysis validated results whole, while quantitative polymerase chain reaction confirmed downregulation miR-122-5p, miR-625-5p, miR-30e-5p upregulation miR-21-5p miR-221-3p. Pathway integrated miRNA/mRNA network identified pathways predominantly involved extracellular matrix function. A number currently available therapies target products upregulated genes network, these being more peripheral members network. The identification group miRNA associated may contribute development new therapeutic approaches AS. This study highlights importance systems biology-based complex diseases.