ACAD8 deficiency promotes pathological cardiac hypertrophy in response to pressure overload [Bulk RNA-seq]
To investigate the molecular mechanisms underlying ACAD8 deficiency-mediated cardiac hypertrophy and the role of histone isobutyrylation in transcriptional regulation, we performed RNA-sequencing across four experimental settings. First, neonatal rat cardiomyocytes (NRCMs) were treated with isobutyrate or PBS (3 vs. 3) to assess the direct effects of isobutyryl-CoA accumulation. Second, left ventricles from cardiomyocyte-specific Acad8 knockout (Acad8cKO) mice and control (Myh6-Cre) mice were collected 4 weeks after transverse aortic constriction (TAC) or sham surgery, with samples comprising TAC groups (5 vs. 6) and sham groups (4 vs. 4). Third, an AAV9-mediated ACAD8 overexpression model was established in mice subjected to TAC for 1 week followed by 3 weeks of overexpression, with AAV9-Ctrl-TAC and AAV9-ACAD8-TAC groups (4 vs. 4). This dataset provides comprehensive transcriptomic profiles revealing that ACAD8 deficiency enhances histone isobutyrylation and promotes hypertrophy-related gene expression, whereas ACAD8 overexpression reverses these transcriptional changes, offering insights into the role of branched-chain amino acid metabolism in cardiac pathology.