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Identification of FDA-approved drugs that induce heart regeneration in mammals.
Ahmed, Mahmoud Salama; Nguyen, Ngoc Uyen Nhi; Nakada, Yuji; Hsu, Ching-Cheng; Farag, Ayman; Lam, Nicholas T; Wang, Ping; Thet, Suwannee; Menendez-Montes, Ivan; Elhelaly, Waleed M; Lou, Xi; Secco, Ilaria; Tomczyk, Mateusz; Zentilin, Lorena; Pei, Jimin; Cui, Miao; Dos Santos, Matthieu; Liu, Xiaoye; Liu, Yan; Zaha, David; Walcott, Gregory; Tomchick, Diana R; Xing, Chao; Zhang, Cheng Cheng; Grishin, Nick V; Giacca, Mauro; Zhang, Jianyi; Sadek, Hesham A.
Afiliação
  • Ahmed MS; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Nguyen NUN; These authors contributed equally: Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen.
  • Nakada Y; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Hsu CC; These authors contributed equally: Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen.
  • Farag A; Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Lam NT; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Wang P; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Thet S; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Menendez-Montes I; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Elhelaly WM; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Lou X; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Secco I; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Tomczyk M; Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Zentilin L; School of Cardiovascular and Metabolic Medicine & Sciences and British Heart Foundation Centre of Research Excellence, King's College London, London, UK.
  • Pei J; School of Cardiovascular and Metabolic Medicine & Sciences and British Heart Foundation Centre of Research Excellence, King's College London, London, UK.
  • Cui M; Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
  • Dos Santos M; Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Liu X; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Liu Y; Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Zaha D; Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Walcott G; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Tomchick DR; Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Xing C; Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Zhang CC; Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Grishin NV; Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Giacca M; Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Zhang J; Division of Cardiovascular Diseases, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Sadek HA; Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Cardiovasc Res ; 3(3): 372-388, 2024 Mar.
Article em En | MEDLINE | ID: mdl-39183959
ABSTRACT
Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro-Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals País/Região como assunto: America do norte Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals País/Região como assunto: America do norte Idioma: En Ano de publicação: 2024 Tipo de documento: Article