Identifying the expression and role of lncRNA in regulating hypertrophic cardiomyopathy

Background: Although long non-coding RNA (lncRNA) transcripts do not code for proteins, they have important biological roles like transcriptional and translational regulation. Despite a growing body of knowledge on the biological function of lncRNAs, their role in regulating hypertrophic cardiomyopathy (HCM), a cardiovascular disease marked by left ventricular (LV) hypertrophy, remains incompletely understood. Hypothesis: We hypothesize that lncRNAs are differentially expressed in an HCM model and affect HCM pathophysiology. Methods and Results: LV tissue from 64 mice that are transgenic (TG) or non-transgenic (nTG) for the ∆160 cTnT HCM variant were subject to bulk RNA-Seq. Bioinformatic analysis revealed the expression of 9,140 known and potentially novel lncRNA genes. Differential expression (DE) analysis identified 38 of those genes that show any level of DE with a Benjamini-Hochberg adjusted p -value ≤ 0.05 among different comparison groups including TG vs nTG. Additional filtering was conducted to only include genes with human orthologs. Strand-specific RT-qPCR is now being validated on four genes that pass these criteria, with the goal of recreating the results from RNA-Seq and validating the RT-qPCR assay for future use. Conclusions and future directions: This study is ongoing, but our preliminary results show that there are many lncRNA genes that demonstrate highly significant DE within a murine HCM model. Once the RT-qPCR assays are validated, lncRNAs with higher expression among TG mice will be knocked-down and conversely, lncRNAs with lower expression among TG mice will be over-expressed. Mice will then be subject to phenotypic and transcriptomic screening to identify a potential rescue of disease phenotype. Institutional/internal grants This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.