Language
English
Publication Date
12-8-2020
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2011614117
PMID
33229578
PMCID
PMC7733826
PubMedCentral® Posted Date
11-23-2020
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Animals, Cell Differentiation, Cyclohexanones, Fibroblasts, Fibrosis, Heart Function Tests, Inflammation, Macrophages, Mice, Myocardial Infarction, Pyridines, RAW 264.7 Cells, RNA, Receptors, Steroid, Transcription, Genetic, Ventricular Remodeling
Published Open-Access
yes
Recommended Citation
Mullany, Lisa K; Rohira, Aarti D; Leach, John P; et al., "A Steroid Receptor Coactivator Stimulator (Mcb-613) Attenuates Adverse Remodeling After Myocardial Infarction" (2020). Faculty and Staff Publications. 311.
https://digitalcommons.library.tmc.edu/baylor_docs/311
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Cardiology Commons, Cardiovascular Diseases Commons, Medical Sciences Commons