Acetyltransferase p300 Inhibitor Reverses Hypertension-Induced Cardiac Fibrosis

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

J Cell Mol Med. 2019 Apr;23(4):3026-3031.

PMID: 30710427

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP321695572	L002		321695-57-2	Price