Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 1;10(1):6.
doi: 10.1186/s13619-020-00068-y.

Vertebrate cardiac regeneration: evolutionary and developmental perspectives

Affiliations
Review

Vertebrate cardiac regeneration: evolutionary and developmental perspectives

Stephen Cutie et al. Cell Regen. .

Abstract

Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures, and as members of certain species developmentally progress towards their adult forms. While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults, neonates of these same species can fully regenerate heart structure and function after injury - as can adult lower vertebrates like many teleost fish and urodele amphibians. Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally: an oxygen-rich environment, vertebrate thermogenesis, a complex adaptive immune system, and cancer risk trade-offs. In this review, we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.

Keywords: Cardiomyocyte proliferation; Cell cycle arrest; Development; Endothermy; Evolution; Heart; Inflammation; Polyploidization; Regeneration.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Visual representation of four major hypotheses of drivers of vertebrate cardiac regenerative potential loss in evolution and development

References

    1. Arslan F, et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel antitoll-like receptor-2 antibody. Circulation. 2010;121:80–90. - PubMed
    1. Ashaolu JO, Ajao MS. Cardiac adaptation in prolonged inverted bats (Eidolon helvum) Eur J Anat. 2014;18:283–290.
    1. Aurora AB, Olson EN. Immune modulation of stem cells and regeneration. Cell Stem Cell. 2014;15:14–25. - PMC - PubMed
    1. Aurora AB, et al. Macrophages are required for neonatal heart regeneration. J Clin Invest. 2014;124:1382–1392. - PMC - PubMed
    1. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P. Evidence that human cardiac myocytes divide After myocardial infarction. N Engl J Med. 2001;344:1750–1757. - PubMed