Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis

Rahul Rai, Tianjiao Sun, Veronica Ramirez, Elizabeth Lux, Mesut Eren, Douglas E. Vaughan, Asish K. Ghosh*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Epigenetic dysregulation plays a crucial role in cardiovascular diseases. Previously, we reported that acetyltransferase p300 (ATp300) inhibitor L002 prevents hypertension-induced cardiac hypertrophy and fibrosis in a murine model. In this short communication, we show that treatment of hypertensive mice with ATp300-specific small molecule inhibitor L002 or C646 reverses hypertension-induced left ventricular hypertrophy, cardiac fibrosis and diastolic dysfunction, without reducing elevated blood pressures. Biochemically, treatment with L002 and C646 also reverse hypertension-induced histone acetylation and myofibroblast differentiation in murine ventricles. Our results confirm and extend the role of ATp300, a major epigenetic regulator, in the pathobiology of cardiac hypertrophy and fibrosis. Most importantly, we identify the efficacies of ATp300 inhibitors C646 and L002 in reversing hypertension-induced cardiac hypertrophy and fibrosis, and discover new anti-hypertrophic and anti-fibrotic candidates.

Original languageEnglish (US)
Pages (from-to)3026-3031
Number of pages6
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number4
DOIs
StatePublished - Apr 2019

    Fingerprint

Keywords

  • acetyltransferase p300
  • cardiac fibrosis
  • cardiac hypertrophy
  • collagens
  • epigenetics
  • hypertension
  • small molecule inhibitors of p300

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this