Abstract 12545: Ross Autograft Leaflet Response to Systemic Circulation: Expression Profiling Reveals Divergence From Normal Aortic and Pulmonary Valve Leaflets

IntroductionThe Ross procedure has been employed for many years as treatment for aortic valve disease. It is a unique surgery in that the pulmonary valve, which is inherently designed to support low pressure pulmonary circulation, is placed in the aortic valve position; thus, supporting high pressure systemic circulation. It is incompletely understood how the Ross valve leaflet genes respond to the altered mechanical stresses. We examined gene expression patterns in explanted Ross autograft valves (RG) and compared them to normal pulmonary (PV) and aortic valves (AV), and regurgitant aortic valves (AR).MethodsRoss valves (RG; n=4), normal pulmonic valves (PV; n=5), normal aortic valves (AV; n=5), and regurgitant aortic valves (AR; n=6) were studied; no non-diseased RG were available for analysis. Total RNA was extracted from human leaflet tissues and underwent commercial RNA-sequencing analysis (Novogene). Unbiased statistical analysis compared transcriptome profiles of the four groups.ResultsClustering analysis demonstrated that PV was intermediate in relation to AV and RG; an unanticipated finding. Pairwise comparisons revealed that among the 11 most up-regulated genes, 9 were common to both RG/AV and RG/PV groups with RG/AV showing consistently higher fold-change in expression (range 7 to 42-fold) vs RG/PV (range 7 to 15-fold). The top 3 gene ontology representations are related to extracellular matrix. Intriguingly, comparing these RG top up- and down-regulated genes with those expressed by AR-patient AV reveals that the highest-regulated genes among RG and AR are identical.ConclusionPulmonary valves implanted in the aortic position that become regurgitant exhibit differentially regulated genes compared with normal AV and PV; specifically, genes that mediate extracellular matrix remodeling. This pattern of expressed genes is also present in AR leaflets; supporting the concept that adaptation of the RG emphasizes extracellular matrix remodeling distinct from normal AV or PV but similar to AR. We conclude that Ross autografts explanted due to AR resemble a native regurgitant aortic valve from the perspective of matrix modification genes.