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Stimulating ideas for heart regeneration: the future of nerve-directed heart therapy
Emma B Brandt1, S Janna Bashar1, Ahmed I Mahmoud1
1Department of Cell and Regenerative Biology, University of Wisconsin-Madison School of Medicine and Public Health, 1111 Highland Ave, Room 4557, Madison, WI 53705 USA.
Insights
Cholinergic nerve signaling is crucial for neonatal mouse heart regeneration. Understanding these mechanisms could lead to new bioelectronic therapies for heart disease, improving cardiac repair.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Neuroscience
Background:
- Ischemic heart disease causes significant mortality, leading to cardiomyocyte death and heart failure.
- Adult hearts lack regenerative capacity, unlike neonatal hearts which exhibit limited regeneration.
- Current treatments for heart damage are insufficient to restore lost cardiomyocytes or prevent scarring.
Purpose of the Study:
- To review the role of nerve signaling in cardiac regeneration across species.
- To explore the specific mechanisms of cholinergic innervation in neonatal heart regeneration.
- To highlight the potential of bioelectronic therapies for treating heart disease.
Main Methods:
- Review of historical and recent scientific literature on nerve function and cardiac regeneration.
- Focus on studies investigating cholinergic signaling pathways in the context of cardiomyocyte proliferation and inflammation.
- Analysis of mechanisms underlying neonatal cardiac repair versus adult cardiac remodeling.
Main Results:
- Cholinergic nerve signaling is essential for the regenerative capacity observed in neonatal mouse hearts.
- This signaling pathway influences cardiomyocyte proliferation and modulates inflammatory responses post-injury.
- Neonatal regeneration is restricted to a narrow developmental window.
Conclusions:
- Cholinergic nerve stimulation presents a promising bioelectronic therapeutic strategy for heart disease.
- Further research into nerve-directed regeneration mechanisms is needed to develop effective treatments.
- Understanding these pathways could revolutionize the approach to treating heart failure and promoting cardiac repair.
Abstract:
Ischemic heart disease is the leading cause of death worldwide. The blockade of coronary arteries limits oxygen-rich blood to the heart and consequently there is cardiomyocyte (CM) cell death, inflammation, fibrotic scarring, and myocardial remodeling. Unfortunately, current therapeutics fail to effectively replace the lost cardiomyocytes or prevent fibrotic scarring, which results in reduced cardiac function and the development of heart failure (HF) in the adult mammalian heart. In contrast, neonatal mice are capable of regenerating their hearts following injury. However, this regenerative response is restricted to the first week of post-natal development. Recently, we identified that cholinergic nerve signaling is necessary for the neonatal mouse cardiac regenerative response. This demonstrates that cholinergic nerve stimulation holds significant potential as a bioelectronic therapeutic tool for heart disease. However, the mechanisms of nerve directed regeneration in the heart remain undetermined. In this review, we will describe the historical evidence of nerve function during regeneration across species. Specifically, we will focus on the emerging role of cholinergic innervation in modulating cardiomyocyte proliferation and inflammation during heart regeneration. Understanding the role of nerves in mammalian heart regeneration and adult cardiac remodeling can provide us with innovative bioelectronic-based therapeutic approaches for treatment of human heart disease.
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