Comparative transcriptome profiling in @entity1 XXXX using RNA-sequencing.

@entity4503 @entity1 @entity16491 @entity41277 @entity7874 @entity340
UNASSIGNED: Intrinsic @entity340 is the most common complication of @entity4503 . Phenotypically, it ranges from @entity7874 to redundant or prolapsing regurgitant leaflets. The underlying molecular mechanism underpinning phenotype heterogeneity of @entity340 in BAV is poorly understood. We used RNA-sequencing to identify genes and pathways responsible for @entity340 in BAV, compared to tricuspid aortic valve ( @entity16491 ). Comparative transcriptome analysis on total RNA of aortic valve tissues of @entity1 with diseased BAV (n=5) and calcified @entity16491 (n=3). A total of 59 and 177 genes were significantly up- and downregulated, respectively, in BAV compared to @entity16491 . Hierarchical clustering indicated heterogeneity within the BAV group, separating those with heavy calcification (BAVc) from those with redundant leaflets and/or minimal calcification (BAVr). Interestingly, the gene expression profile of the BAVc group closely resembled the @entity16491 , with shared up- and downregulation of inflammatory and NOTCH1 signaling pathways, respectively. Downregulation of matrix protease ADAMTS9 and protein aggrecan were observed in BAVr compared to @entity16491 . Dysregulation of fetal gene programs were also present, with notable downregulation of SEMA6B and SEMA3F in BAVr and BAVc compared to @entity16491 , respectively. Upregulation of @entity41277 was observed exclusively in BAVr compared to BAVc. In conclusion, diverging molecular mechanisms underpin phenotype heterogeneity of @entity340 in BAV and data from the present study suggest that there may be shared mechanisms leading to calcification in BAV and @entity16491 . Recognition of these pathways is fundamental to improve our understanding of the molecular basis of @entity1 @entity4503 .
