AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo

Byung Hyun Cha, Minjin Jung, Angela S. Kim, Victoria C. Lepak, Brett A. Colson, David A. Bull, Youngwook Won

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiac hypertrophy is one of the most common genetic heart disorders and considered a risk factor for cardiac morbidity and mortality. The mammalian target of rapamycin (mTOR) pathway plays a key regulatory function in cardiovascular physiology and pathology in hypertrophy. AZD2014 is a small-molecule ATP competitive mTOR inhibitor working on both mTORC1 and mTORC2 complexes. Little is known about the therapeutic effects of AZD2014 in cardiac hypertrophy and its underlying mechanism. Here, AZD2014 is examined in in vitro model of phenylephrine (PE)-induced human cardiomyocyte hypertrophy and a myosin-binding protein-C (Mybpc3)-targeted knockout (KO) mouse model of cardiac hypertrophy. Our results demonstrate that cardiomyocytes treated with AZD2014 retain the normal phenotype and AZD2014 attenuates cardiac hypertrophy in the Mybpc3-KO mouse model through inhibition of dual mTORC1 and mTORC2, which in turn results in the down-regulation of the Akt/mTOR signaling pathway.

Original languageEnglish (US)
Article number24
JournalJournal of Biological Engineering
Volume15
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • AZD2014
  • Cardiac hypertrophy
  • Cardiomyocyte
  • mTOR inhibitor

ASJC Scopus subject areas

  • Environmental Engineering
  • Biomedical Engineering
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo'. Together they form a unique fingerprint.

Cite this