Abstract 19210: Altered Micrornas In Bicuspid Aortic Valve
Background: MicroRNAs (miRNAs) have been shown to modulate gene expression. This study examined miRNAs that were altered in bicuspid aortic valve and evaluated the differentially expressed miRNAs in BAV with Stenosis (AS) as compared to insufficiency (AI). Additionally, in vitro experiments were performed to examine if altered miRNAs found in BAV modulate calcification-related genes.
Materials and Methods: Aortic valve samples (fused or unfused leaflets) were collected from nine patients (mean age 44.9±13.8 years) undergoing aortic valve replacement. PIQORTM miRXplore Microarrays containing 1421 miRNAs were used. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the miRNA array results. Cultured human aortic valve cells (AVICs) were treated with miRNA mimics and qRT-PCR was performed to determine changes in mRNAs. Results_Seven miRNAs were statistically different between the AS and AI patients by microarray. MiR-26a and miR-195 levels were reduced by 65% and 59% respectively with p<0.05 in the stenotic samples by qRT-PCR. Human AVICs treated with miR-26a or miR-30b mimics had decreased mRNA levels of calcification-related genes. MiR-26a repressed BMP2 by 36%, ALKALINE PHOSPHATASE by 38%, and SMAD1 by 26%. MiR-30b reduced expression of SMAD1 by 18% and SMAD3 by 12%. Whereas miR-195 treated AVICs had increased mRNA levels of calcification-related genes such as BMP2 by 68% and RUNX2 by 11%.
Conclusion: MiR-26a, miR-30b, and miR-195 were decreased in the aortic valves of patients requiring valve replacement due to AS compared to those being replaced due to AI. These miRNAs appear to modulate calcification related genes in vitro.
- © 2010 by American Heart Association, Inc.