A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction

Lisa K. Mullany, Aarti D. Rohira, John P. Leach, Jong H. Kim, Tanner O. Monroe, Andrea R. Ortiz, Brittany Stork, M. Waleed Gaber, Poonam Sarkar, Andrew G. Sikora, Todd K. Rosengart, Brian York, Yongcheng Song, Clifford C. Dacso, David M. Lonard, James F. Martin, Bert W. O'Malley

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion of Tsc22d3-expressing macrophages-all of which may limit inflammatory damage. SRC stimulation with MCB-613 (and derivatives) is a potential therapeutic approach for inhibiting cardiac dysfunction after MI.

Original languageEnglish (US)
Pages (from-to)31353-31364
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number49
DOIs
StatePublished - Dec 8 2020

Keywords

  • Fibrosis
  • MCB-613
  • Myocardial infarction

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction'. Together they form a unique fingerprint.

Cite this