Microarray Gene Expression Profiles In Left Ventricular Failure Resulting From Severe Aortic Valve Stenosis

OBJECTIVES: In this study our goals were to establish wholegenomic gene expression profiles of Left ventricular hypertrophy resulting from severe aortic valve stenosis(and/or slight regurgitation) to screen target genes relating to left ventricular hypertrophy resulted from aortic valve stenosis and to discover potential etiologies in the development of the syndrome.METHODS: Firstly, the gene expression profiles of the left ventricular myocardium obtained from cases with Left ventricular hypertrophy resulting from severe aortic valve stenosis(and/or slight regurgitation) and normal control were profiled by using four human whole-genomic obligonucleotide microarrays(HG U133 Plus 2.0 GeneChip). Between two groups of the fingerprints, GeneSpring software was performed to screen the markedly differentially expressed genes or expressed sequences tags(ESTs)as the target genes relating to Left ventricular hypertrophy resulting from severe aortic valve stenosis. Secondly, Realtime-Time PCR was carried out to validate the expression of 2 target genes. Based on the results, novel potential etiologies in the development of Left ventricular hypertrophy resulting from severe aortic valve stenosis.RESULTS: The results of quality control inspection certified the qualification of the cRNA product purified from the left ventricular myocardium of two sample groups. Then, the original data were fed into the bioinformatics software GeneSpring. After data normalization, grouped comparisons by were applied to compare the difference between the microarray data of two sample groups.145 probe sets of genes or ESTs were determined to be the target genes relating to Left ventricular remodeling and failure resulting from aortic valve stenosis and regurgitation, according to the statistical cutoff point whose value was blow0.01 and Fold Change(FC) beyond2.0.The relative abundance of 2 targeted genes(COL1A1 gene and JARID2 gene)relating to Left ventricular hypertrophy resulting from severe aortic valve stenosis,were detetcted in two sample groups by RealTime PCR. COL1A1 gene was 3.39-fold upregulated and JARID2 was 0.36-fold downregulated.In the left ventricular myocardium samples of experimental group(Left ventricular hypertrophy resulting from severe aortic valve stenosis) vs normal controlled group.The reliability of microarray detection was reinforced by the consistency that the results of validation by RealTime PCR were coincided with the findings detectedby gene microarrays.CONCLUSION: Studies of the expression fingerprints for the gene clusters relating to Left ventricular hypertrophy resulting from severe aortic valve stenosis, which may be involved in the genesis and development of the syndrome, are helpful for the understanding of its pathogenesis and pathophysiology. The Real Time analysis of the whole-genomic gene expression profile by microarray is denmenstrated to be an advanced technique for high-throughput screening of the related gene clusters of Left ventricular hypertrophy resulting from severe aortic valve stenosis.80 target genes relating to Left ventricular hypertrophy resulting from severe aortic valve stenosis were determined, in which 50 were observed up-regulated such as NPPB and IGFBP2 genes,and 30 were down-regulated such as FOS and CORIN, for the first time, in the left ventricular myocardium obtained from cases with Left ventricular hypertrophy resulting from severe aortic valve stenosis (and/or slight regurgitation)vs normal control. All the results provide important predictive informatiom for further study on the genetic markers and molecular mechanisms leading to the syndrome.