학술논문
A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction.
Document Type
Academic Journal
Author
Mullany LK; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Rohira AD; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Leach JP; Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Kim JH; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, TX 77030.; Cardiomyocyte Renewal Lab, Texas Heart Institute, Houston, TX 77030.; Monroe TO; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, TX 77030.; Ortiz AR; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Stork B; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Gaber MW; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.; Sarkar P; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.; Sikora AG; Department of Otolaryngology-Head & Neck Surgery, Baylor College of Medicine, Houston, TX 77030.; Rosengart TK; Department of Surgery, Baylor College of Medicine, Houston, TX 77030.; York B; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Song Y; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030.; Dacso CC; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Lonard DM; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.; Martin JF; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, TX 77030; jfmartin@bcm.edu berto@bcm.edu.; Cardiomyocyte Renewal Lab, Texas Heart Institute, Houston, TX 77030.; O'Malley BW; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; jfmartin@bcm.edu berto@bcm.edu.
Source
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: The authors declare no competing interest.
(Copyright © 2020 the Author(s). Published by PNAS.)
Competing Interests: The authors declare no competing interest.
(Copyright © 2020 the Author(s). Published by PNAS.)