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ACAD8 deficiency promotes pathological cardiac hypertrophy in response to pressure overload by regulating histone isobutyrylation - PubMed

3 hours ago
  • #histone modification
  • #cardiac hypertrophy
  • #metabolic regulation
  • ACAD8 deficiency in male mice worsens cardiac hypertrophy and dysfunction under pressure overload.
  • Deficiency leads to accumulation of isobutyryl-CoA, increasing histone isobutyrylation, chromatin accessibility, and TEAD2 binding at hypertrophy-related gene promoters.
  • Overexpression of ACAD8 in cardiomyocytes reduces isobutyryl-CoA and histone isobutyrylation, mitigating cardiac hypertrophy and dysfunction.
  • Findings link ACAD8 deficiency to cardiomyopathy via histone isobutyrylation-mediated transcription regulation.