Author + information
- Katsuhide Maeda,
- Xiaoyuan Ma,
- Christina L. Greene,
- Frank L. Hanley and
- R. Kirk Riemer
Background: Mechanisms of AR or AS disease progression at gene level are not known. In an ex vivo Rat AV bioreactor model we reported that whether the primary issue is regurgitation or stenosis, AV leaflets undergo profound alteration in gene regulation when coaptation is impaired. We analyzed human AR and AS leaflet gene patterns and observed distinctly different patterns of expression, as we see in our bioreactor model.
Methods: Whole transcriptome gene array interrogation was used to assess mRNA expression in Normal, AR and AS patients (N=5-8/ group). Partek analysis software was used to compare changes in gene expression and conduct hierarchical clustering analysis.
Results: Comparison of expression levels using heat mapping (Figure) demonstrates an apparent gradient in gene regulation from Normal to AR to AS: 325 regulated genes (> 2-fold, P<0.05). We identified >25 genes that were most activated in AS while >30 genes were most deactivated in AS. Expression in AR was intermediate for these 55 genes.
Conclusions: Considering the expression pattern difference among the 3 groups, a distinct gradient in up or down regulation is evident from heat mapping. Though AS and AR are distinct diseases, from the perspective of AV leaflets, AR and AS may comprise a continuum of disturbed mechanical homeostatic cues evidenced by altered expression of a subset of genes. Identifying the regulatory mechanisms for these genes will advance our understanding of the effects of mechanical forces on valve homeostasis.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Valvular Heart Disease: Aortic Regurgitation
Abstract Category: 36. Valvular Heart Disease: Clinical
Presentation Number: 1184-025
- 2017 American College of Cardiology Foundation