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Published on: June 3, 2018
Mending a broken heart-targeting cardiomyocyte regeneration: a literature review
Chunna Jin1, Shiyu Zhu1, Tingting Zhao1
1Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Insights
Adult mammalian hearts have limited cardiomyocyte regeneration due to barriers like polyploidy. Strategies such as resident cardiomyocyte activation and reprogramming offer new hope for heart regeneration therapies.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
Background:
- Cardiovascular diseases are a leading global cause of death.
- Current treatments slow disease progression but do not prevent cardiomyocyte loss.
- Heart failure remains an inevitable end stage for many cardiovascular diseases.
Purpose of the Study:
- To review key biomedical findings in cardiomyocyte regeneration.
- To explore underlying principles and emerging strategies for heart regeneration.
Main Methods:
- Comprehensive literature search of PubMed and Web of Science databases.
- Focused on research concerning cardiomyocyte regeneration, its controversies, barriers, and strategies.
- Included studies on animal models and methodologies in heart regeneration research.
Main Results:
- Adult mammalian cardiomyocytes have limited proliferation capacity, with most new cells arising from existing cardiomyocytes, not cardiac progenitor cells (CPCs).
- Barriers to regeneration include metabolic shifts, polyploidy, epigenetic/transcriptomic alterations, and immune system evolution.
- Emerging strategies involve activating resident cardiomyocytes, somatic cell reprogramming, and promoting neovascularization and immune modulation.
Conclusions:
- Despite challenges, understanding of adult mammalian cardiac regeneration is advancing.
- New therapeutic avenues for heart regeneration are emerging.
- Cardiomyocyte regeneration holds promise for treating heart failure.
Background And Objectives:
Cardiovascular diseases have been the leading cause of death globally for decades. Pharmacological advances targeting the sympathetic nervous system, renin-angiotensin-aldosterone system, and fibrosis slow the progression of diverse cardiovascular diseases. However, ongoing cardiomyocyte loss is inevitable in divergent cardiovascular diseases, eventually leading to heart failure as the end stage. In this review, we focused on the key biomedical findings and underlying principles of cardiomyocyte regeneration.
Methods:
Literature regarding the key findings in cardiomyocyte regeneration research, including controversies on the origins of newly formed cardiomyocytes, potential barriers and strategies to heart regeneration, and the key animals, models, and methods applied in the study of heart regeneration, were broadly researched using the PubMed and Web of Science databases.
Key Content And Findings:
In the mammalian heart, cardiomyocytes proliferate during the embryonic and early postnatal stages, while the capability of proliferation disappears in the adult stage. An increasing amount of evidence suggests that cardiomyocytes self-renew at a very limited level and that most newly formed cardiomyocytes originate from pre-existing cardiomyocytes and not cardiac progenitor cells (CPCs). Several potential barriers to heart regeneration have been addressed, including metabolic switch, a large increase in multinucleated and polyploid cardiomyocytes, and alteration in the epigenome and transcriptome. In addition, immune system evolution is also associated with the loss of regenerative capacity. However, the activation of resident cardiomyocytes, somatic cell reprogramming, and direct reprogramming, in addition to the promotion of neovascularization and immune modulation, constitute the new insights into those strategies that can boost cardiac regeneration.
Conclusions:
Heart regeneration is one of the most popular fields in cardiovascular research and represents a promising avenue of therapeutics for mending a broken heart. Despite the controversies and challenges, a clearer picture of adult mammalian cardiac regeneration is emerging.
