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 1 2019

Fingerprint

Cardiomegaly
Fibrosis
Hypertension
Epigenomics
Myofibroblasts
Left Ventricular Hypertrophy
Acetylation
Histones
Cardiovascular Diseases
Blood Pressure
p300-CBP-associated factor

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

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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.",
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Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis. / Rai, Rahul; Sun, Tianjiao; Ramirez, Veronica; Lux, Elizabeth; Eren, Mesut; Vaughan, Douglas E; Ghosh, Asish K.

In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 4, 01.04.2019, p. 3026-3031.

Research output: Contribution to journalArticle

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T1 - Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis

AU - Rai, Rahul

AU - Sun, Tianjiao

AU - Ramirez, Veronica

AU - Lux, Elizabeth

AU - Eren, Mesut

AU - Vaughan, Douglas E

AU - Ghosh, Asish K

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