Related Experiment Video
Updated: May 28, 2026
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Beyond Reperfusion: Early Molecular Drivers and Therapeutic Opportunities in Acute Post-Infarction Cardiac Fibrosis
Desaree Tan1, Yi Ee Lye1, Pranjal Patel1
1Inflammation and Cardiovascular Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Insights
Acute myocardial infarction can lead to heart failure due to cardiomyocyte death and fibrosis. Early, cell-targeted interventions like RNA therapies show promise for preserving salvageable myocardium and improving patient outcomes.
Area of Science:
- Cardiology
- Molecular Biology
- Translational Medicine
Background:
- Heart failure, a major global health burden, frequently follows acute myocardial infarction.
- Current treatments like percutaneous coronary intervention do not prevent cardiomyocyte death or post-infarct fibrosis.
- Limited antifibrotic therapies highlight a critical unmet need in managing heart failure progression.
Purpose of the Study:
- To review molecular mechanisms of post-infarct fibrosis.
- To explore potential therapeutic interventions for heart failure development.
- To identify emerging strategies for improved therapeutic precision.
Main Methods:
- Literature review integrating molecular mechanisms of fibrosis.
- Analysis of preclinical and clinical data on anti-inflammatory and cell-targeted therapies.
- Evaluation of novel therapeutic approaches such as RNA-based therapies and cardiac reprogramming.
Main Results:
- Post-infarct fibrosis involves redundant, interconnected molecular pathways.
- Anti-inflammatory and cell-targeted therapies show preclinical promise but limited clinical translation.
- Existing therapies often miss the narrow therapeutic window for preserving viable myocardium.
Conclusions:
- A shift towards early, cell-targeted interventions is crucial for preventing heart failure progression.
- Novel strategies like RNA-based therapies offer enhanced precision for myocardial salvage.
- Improved therapeutic strategies aim to prevent heart failure and enhance patient quality of life.
Abstract:
Heart failure is a leading cause of global morbidity and mortality, often developing as a consequence of acute myocardial infarction. Current management focuses on timely reperfusion via percutaneous coronary intervention. Yet, this approach fails to prevent the molecular cascades that drive the death of viable yet stressed cardiomyocytes within the infarct and peri-infarct zone. Effective antifibrotic therapies remain limited, highlighting a critical gap in current management strategies. This review aims to integrate current understanding of the molecular mechanisms underpinning post-infarct fibrosis and potential interventions for therapeutic development. This emphasis on molecular death signal activation and cell elimination highlights the redundancy of interconnecting fibrosis pathways. Anti-inflammatory and cell-targeted therapies focussing on oxidative stress and haemodynamic load have demonstrated strong preclinical promise. Yet, these approaches have largely failed to translate into clinical benefit. Overall, these limitations emphasise a narrow therapeutic window for intervention. As such, current therapies often fail to preserve metabolically vulnerable myocardium that remains potentially salvageable. Therefore, emerging approaches including RNA-based therapies, cardiac reprogramming, and targeted delivery systems offer new opportunities to improve therapeutic precision. Collectively, these findings support a shift toward early, cell-targeted intervention strategies. This approach aims to prevent progression to heart failure and increases patient quality of life.
