Aims: Myocardial infarction (MI) is a major cause of death worldwide. Effective treatments are required to improve recovery of cardiac function following MI, with the aim of improving patient outcomes and preventing progression to heart failure. The perfused but hypocontractile region bordering an infarct is functionally distinct from the remote surviving myocardium and is a determinant of adverse remodelling and cardiac contractility. Expression of the transcription factor RUNX1 is increased in the border zone 1-day after MI, suggesting potential for targeted therapeutic intervention.
Objective: This study sought to investigate whether an increase in RUNX1 in the border zone can be therapeutically targeted to preserve contractility following MI.
Methods And Results: In this work we demonstrate that Runx1 drives reductions in cardiomyocyte contractility, calcium handling, mitochondrial density, and expression of genes important for oxidative phosphorylation. Both tamoxifen-inducible Runx1-deficient and essential co-factor common β subunit (Cbfβ)-deficient cardiomyocyte-specific mouse models demonstrated that antagonizing RUNX1 function preserves the expression of genes important for oxidative phosphorylation following MI. Antagonizing RUNX1 expression via short-hairpin RNA interference preserved contractile function following MI. Equivalent effects were obtained with a small molecule inhibitor (Ro5-3335) that reduces RUNX1 function by blocking its interaction with CBFβ.
Conclusions: Our results confirm the translational potential of RUNX1 as a novel therapeutic target in MI, with wider opportunities for use across a range of cardiac diseases where RUNX1 drives adverse cardiac remodelling.
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http://dx.doi.org/10.1093/cvr/cvad107 | DOI Listing |
Sci Rep
December 2024
School of Petroleum Engineering, Xi'an Shiyou University, Xi'an, 710065, China.
Horizontal well hydraulic fracturing technology has significantly enhanced the productivity of shale reservoirs. However, our understanding of the expansion patterns within the complex fracture network and fluid seepage mechanisms under field conditions remains inadequate. Here, this work develops a dynamic geomechanical (DG) model to simulate the complete sequence of operations in hydraulic fracturing.
View Article and Find Full Text PDFElife
December 2024
Department of Computer Science, University of Oxford, Oxford, United Kingdom.
Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic current remodelling. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with pro-arrhythmic heterogeneities are unknown. We aim to provide mechanistic explanations of clinical phenotypes in acute and chronic MI, from ionic current remodelling to ECG and EF, using human electromechanical modelling and simulation to augment experimental and clinical investigations.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: The inflammatory response is associated with cardiac repair and ventricular remodeling after myocardial infarction (MI). The key inflammation regulatory factor thymic stromal lymphopoietin (TSLP) plays a critical role in various diseases. However, its role in cardiac repair after MI remains uncertain.
View Article and Find Full Text PDFJ Plast Reconstr Aesthet Surg
November 2024
Oregon Health and Science University, Division of Plastic and Reconstructive Surgery, Portland, OR, USA; Oregon Health and Science University, Transgender Health Program, Portland, OR, USA. Electronic address:
The long thoracic nerve's (LTN) superficial location on the chest wall renders it vulnerable to iatrogenic injury. Plastic surgeons' gender-affirming mastectomy volumes are rapidly increasing. This operation involves lateral chest contouring placing the distal LTN at risk of injury along the chest wall.
View Article and Find Full Text PDFRecenti Prog Med
December 2024
Ssvd Neurologia cognitivo-comportamentale, Asst Spedali Civili di Brescia.
Our purpose was to evaluate the approach of two different chatbots (ChatGPT and Gemini) to a list of questions about emergency department as a border area between hospital and territory. This study was performed in a single day, on 3 March 2024. Two different questions were sequentially type in Italian language, the same for each chatbot: definition of the emergency department as a border zone in Italy; possible solutions to the previous question.
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