Journal
CARDIOVASCULAR RESEARCH
Volume 118, Issue 7, Pages 1667-1679Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvab214
Keywords
Zebrafish; Heart; Regeneration; Model; Myocardial infarction
Categories
Funding
- Wellcome Trust [108906/B/15/Z]
- British Heart Foundation [FS/19/55/34890, CH/11/2/28733, RG/14/3/30706, RM/17/3/33381, CH/11/1/28798, FS/16/4/31831]
- British Heart Foundation [CH/11/1/28798, FS/16/4/31831] Funding Source: researchfish
- Wellcome Trust [108906/B/15/Z] Funding Source: Wellcome Trust
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While humans cannot regenerate their hearts after injury, zebrafish have the ability to fully recover from cardiac insults. The regeneration process in zebrafish involves multiple tissue responses and gene regulatory patterns, with cardiomyocyte regeneration depending on neovascularization and lymphangiogenesis. Studies in zebrafish have provided insights into the mechanisms of cardiovascular repair and regeneration, which can inform strategies for treating human patients with cardiovascular disease.
While humans lack sufficient capacity to undergo cardiac regeneration following injury, zebrafish can fully recover from a range of cardiac insults. Over the past two decades, our understanding of the complexities of both the independent and co-ordinated injury responses by multiple cardiac tissues during zebrafish heart regeneration has increased exponentially. Although cardiomyocyte regeneration forms the cornerstone of the reparative process in the injured zebrafish heart, recent studies have shown that this is dependent on prior neovascularization and lymphangiogenesis, which in turn require epicardial, endocardial, and inflammatory cell signalling within an extracellular milieu that is optimized for regeneration. Indeed, it is the amalgamation of multiple regenerative systems and gene regulatory patterns that drives the much-heralded success of the adult zebrafish response to cardiac injury. Increasing evidence supports the emerging paradigm that developmental transcriptional programmes are re-activated during adult tissue regeneration, including in the heart, and the zebrafish represents an optimal model organism to explore this concept. In this review, we summarize recent advances from the zebrafish cardiovascular research community with novel insight into the mechanisms associated with endogenous cardiovascular repair and regeneration, which may be of benefit to inform future strategies for patients with cardiovascular disease.
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