Systolic Dysfunction in Infarcted Mice Does Not Necessarily Lead to Heart Failure: Need to Refine Preclinical Models
María Villalba-Orero1, Marina López-Olañeta1, Pablo García-Pavía2,3,4
1Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
Insights
Mouse models with severe cardiac dysfunction after myocardial infarction (MI) do not fully replicate human heart failure (HF). These models lack key HF அறிகுறிகள் like lung congestion, limiting their utility for developing new HF therapies.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Preclinical Models
Background:
- Heart failure (HF) poses a significant global health burden, with limited therapeutic advancements despite high prevalence.
- Myocardial infarction (MI) is a primary cause of human HF, and mouse models are frequently employed to study HF pathophysiology and test interventions.
- Existing preclinical models face limitations, hindering the development of effective HF therapies.
Discussion:
- This study evaluated the validity of mouse MI models for HF research.
- Mice subjected to permanent left coronary artery ligation developed severe, sustained systolic dysfunction and ventricular dilation.
- However, these mice did not exhibit typical HF manifestations such as pulmonary congestion or exercise intolerance over a 10-month period.
Key Insights:
- Severe cardiac dysfunction in mice following MI does not adequately recapitulate the complex syndrome of human heart failure.
- The absence of pulmonary congestion and preserved exercise capacity in these models highlights critical discrepancies.
- These findings underscore the limitations of current mouse MI models in fully representing HF.
Outlook:
- Re-evaluation of current preclinical models is crucial for advancing HF research.
- Development of more comprehensive and translatable HF models is needed.
- Improved models will accelerate the discovery and validation of novel therapeutic strategies for heart failure.
Abstract:
Heart failure (HF) is a major cause of death and hospitalization worldwide. Despite advances in reducing mortality, prognosis remains poor and prevalence has reached epidemic proportions. The limitations of available preclinical models represent a major hurdle in the development of new therapies. Myocardial infarction (MI) is a main cause of HF in humans, and mouse models of MI are often used to study HF mechanisms and experimental treatments. We investigated whether MI in mice constitutes an appropriate model of HF. Permanent ligation of the left coronary artery induced severe and persistent systolic dysfunction and ventricular dilatation. Mouse follow-up for 10 months showed no significant evidence of lung congestion or other pulmonary defects associated with HF. No difference was observed in the capacity of infarcted mice to exercise compared to control animals. These results indicate that severe cardiac dysfunction in mice is not sufficient to demonstrate the presence of HF.
