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Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure
Published on: December 2, 2014
Role of apoptosis in ventricular remodeling
1University of Minnesota, Minneapolis, MN 55417, USA. shekh003@tc.umn.edu
Abstract:
Cell loss is a common feature in the failing heart, and this contributes to the relentless progression seen in patients with heart failure. Apoptosis is one of the most common causes of cell loss in animals and humans with heart failure. There is increasing evidence that apoptosis, even while occurring in a low-grade manner, can mediate heart failure. Moreover, inhibiting apoptosis successfully prevents or attenuates heart failure in several animal models. More importantly, apoptosis is one of the few mechanisms that can be easily modulated using pharmacologic or gene therapy approaches. Animal data, obtained in the past few years, have proven the feasibility and success of this approach toward altering the natural history of heart failure. Human studies are pending, but a number of issues such as the type of inhibitor and its optimum timing/dose will need to be resolved before this becomes a reality. Nevertheless, these data will accrue over time, and anti-apoptotic therapy is likely to emerge as an important form of heart failure therapy.
Insights
Cell loss via apoptosis contributes to heart failure progression. Inhibiting apoptosis shows promise in animal models, suggesting potential for future human heart failure therapies.
Area of Science:
- Cardiology
- Cell Biology
Background:
- Cell loss is a hallmark of heart failure, driving disease progression.
- Apoptosis, or programmed cell death, is a primary mechanism of cell loss in failing hearts.
- Low-grade apoptosis can significantly contribute to the development and severity of heart failure.
Purpose of the Study:
- To review the role of apoptosis in heart failure.
- To evaluate the therapeutic potential of inhibiting apoptosis in heart failure.
Main Methods:
- Review of existing animal model data on apoptosis inhibition in heart failure.
- Analysis of the feasibility and success of pharmacologic and gene therapy approaches.
Main Results:
- Inhibition of apoptosis has successfully prevented or lessened heart failure in multiple animal models.
- Animal studies demonstrate the feasibility of modulating apoptosis to alter heart failure's natural course.
Conclusions:
- Apoptosis is a key, targetable mechanism in heart failure.
- Anti-apoptotic strategies have shown significant promise in preclinical studies.
- Further human studies are needed to optimize anti-apoptotic therapies for clinical use in heart failure.
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