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Background  Aortic valve ( AV ) disease presents critical situations requiring surgery in over 2% of the  US  population and is increasingly the reason for cardiac surgery. Throughout the  AV  cycle, mechanical forces of multiple types and varying intensities are exerted on valve leaflets. The mechanisms whereby forces regulate leaflet homeostasis are incompletely understood. We used a novel flow bioreactor culture to investigate alteration of  AV  opening or closure on leaflet genes.    Methods and Results  Culture of rat  AV  was conducted in a flow bioreactor for 7 days at 37°C under conditions approximating the normal stroke volume. Three force condition groups were compared: Cycling (n=8); always open (Open; n=3); or always closed (Closed; n=5). From each culture,  AV  leaflets were pooled by force condition and  RNA  expression evaluated using microarrays. Hierarchical clustering of 16 transcriptome data sets from the 3 groups revealed only 2 patterns of gene expression: Cycling and Closed groups clustered together, whereas Open  AV  were different ( P <0.05). Sustained  AV  opening induced marked changes in expression (202 transcripts >2‐fold;  P <0.05), whereas Closed  AV  exhibited similar expression pattern as Cycling (no transcripts >2‐fold;  P <0.05). Comparison with human sclerotic and calcific  AV  transcriptomes demonstrated high concordance of >40 Open group genes with progression toward disease.    Conclusions  Failure of  AV  to close initiates an extensive response characterized by expression changes common to progression to calcific aortic valve disease.  AV  coaptation, whether phasic or chronic, preserved phenotypic gene expression. These results demonstrate, for the first time, that coaptation of valve leaflets is a fundamentally important biomechanical cue driving homeostasis.

Critical Role of Coaptive Strain in Aortic Valve Leaflet Homeostasis: Use of a Novel Flow Culture Bioreactor to Explore Heart Valve Mechanobiology