Abstract 16925: Use of a Novel Flow Culture Bioreactor to Examine Effects of Disrupted Coaptive Strain on Mitral Valve Leaflet Homeostasis
Introduction: Mitral valve regurgitation (MR) constitutes an increasing burden of adult and pediatric cardiac disease that tends to worsen over time. Beyond the etiologic factors initiating MR, the effects of impaired coaptation-induced leaflet mechanical force alterations on disease progression is unknown.
Hypothesis: Disruption of mitral valve (MV) leaflet coaptive strain alters the expression of genes critical to leaflet tissue homeostasis.
Methods: A flow-culture bioreactor system was used to maintain rat mitral valves in vitro with either anterograde flow–induced (84 BPM) cyclic coaptation (Cycling valve group; n=5) or in a sustained, unloaded open state (Open valve group n=5). Following 3 days of culture (55mmHg afterload), mitral valve leaflets from each group were analyzed using genome-wide expression microarray.
Results: Over 48 genes exhibited markedly changed expression (>4-fold; P<0.05; Cycling Vs. Open valves) when coaptive leaflet strain was disrupted for only 3 days. We previously reported that aortic valve (AV) leaflet genes showed altered expression when coaptive strain was similarly prevented using this bioreactor culture approach. Of note, disrupted coaptation regulated many of the same genes in both MV and AV leaflets, including Angpt2, Cd74, RT1-Da (HLA-DRA) and Igfbp3. Further, several of these genes exhibit expression changes in published studies of calcific human AV leaflets.
Conclusions: Disruption of normal mitral valve leaflet coaptive strain markedly alters the expression of multiple leaflet genes, indicating that cyclic strain is critically important to sustaining leaflet homeostasis. Further, these results demonstrate a consistent reaction of both aortic and mitral valve leaflets to disruption of their normal cyclic strain pattern, supporting the concept that expediting the restoration of normal leaflet coaptive strain is critically important to valve homeostasis as well as systemic hemodynamics. Congruent gene regulation among valves with disrupted strain patterns implicates strain as a common factor potentially unifying valve diseases of heterologous etiology but characterized by disrupted coaptation.
Author Disclosures: K. Maeda: None. X. Ma: None. F.L. Hanley: None. R.K. Riemer: None.
- © 2016 by American Heart Association, Inc.