Limits...
Integrated microRNA and messenger RNA analysis in aortic stenosis

View Article: PubMed Central - PubMed

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.

No MeSH data available.


microRNA expression in aortic valve tissue as measured by quantitative polymerase chain reaction.Abbreviations: n.s., not significant. Symbols: *p < 0.05; **p < 0.01; ***p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120312&req=5

f3: microRNA expression in aortic valve tissue as measured by quantitative polymerase chain reaction.Abbreviations: n.s., not significant. Symbols: *p < 0.05; **p < 0.01; ***p < 0.0001.

Mentions: To validate specific miRNAs, qPCR was used to examine 16 severely diseased samples and 36 control samples (including the original 15 severely diseased samples and 16 control samples) (Fig. 3). Comparing the AS to control groups, we confirmed differences in levels of miR-122-5p (Mann-Whitney p < 0.0001), miR-21-5p (p < 0.0001), miR-625-5p (p = 0.017), miR-221-3p (p < 0.0001) and miR-30e-5p (p = 0.012). miR-200c-3p levels were statistically different (p = 0.001), but in the opposite direction to the microarray results (up-regulated in diseased AS samples by qPCR analysis), while validation qPCR of miR-486-5p showed no difference between the two groups (p = 0.74).


Integrated microRNA and messenger RNA analysis in aortic stenosis
microRNA expression in aortic valve tissue as measured by quantitative polymerase chain reaction.Abbreviations: n.s., not significant. Symbols: *p < 0.05; **p < 0.01; ***p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120312&req=5

f3: microRNA expression in aortic valve tissue as measured by quantitative polymerase chain reaction.Abbreviations: n.s., not significant. Symbols: *p < 0.05; **p < 0.01; ***p < 0.0001.
Mentions: To validate specific miRNAs, qPCR was used to examine 16 severely diseased samples and 36 control samples (including the original 15 severely diseased samples and 16 control samples) (Fig. 3). Comparing the AS to control groups, we confirmed differences in levels of miR-122-5p (Mann-Whitney p < 0.0001), miR-21-5p (p < 0.0001), miR-625-5p (p = 0.017), miR-221-3p (p < 0.0001) and miR-30e-5p (p = 0.012). miR-200c-3p levels were statistically different (p = 0.001), but in the opposite direction to the microarray results (up-regulated in diseased AS samples by qPCR analysis), while validation qPCR of miR-486-5p showed no difference between the two groups (p = 0.74).

View Article: PubMed Central - PubMed

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&thinsp;&lt;&thinsp;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.

No MeSH data available.