Skip to main page content
U.S. flag
See More

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
. 2014 Nov;13(3 Pt B):556-70.
doi: 10.1016/j.scr.2014.06.003. Epub 2014 Jul 9.

A neonatal blueprint for cardiac regeneration

Enzo R Porrello  1 , Eric N Olson  2
Affiliations
Review

A neonatal blueprint for cardiac regeneration

Enzo R Porrello et al. Stem Cell Res. 2014 Nov.

Abstract

Adult mammals undergo minimal regeneration following cardiac injury, which severely compromises cardiac function and contributes to the ongoing burden of heart failure. In contrast, the mammalian heart retains a transient capacity for cardiac regeneration during fetal and early neonatal life. Recent studies have established the importance of several evolutionarily conserved mechanisms for heart regeneration in lower vertebrates and neonatal mammals including induction of cardiomyocyte proliferation, epicardial cell activation, angiogenesis, extracellular matrix deposition and immune cell infiltration. In this review, we provide an up-to-date account of the molecular and cellular basis for cardiac regeneration in lower vertebrates and neonatal mammals. The historical context for these recent findings and their ramifications for the future development of cardiac regenerative therapies are also discussed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Different injury models for studies of cardiac regeneration in the newt, zebrafish and neonatal mouse. Cardiomyocyte proliferative responses (localized or global) and the outcomes of genetic lineage tracing experiments are highlighted. Green dots denote proliferating cardiomyocytes.
Figure 2
Figure 2
Molecular and cellular mechanisms of cardiac regeneration in adult zebrafish. Retinoic acid (RA) is produced and released by epicardial and endocardial cells shortly after injury and acts on cardiomyocytes to induce proliferation. Other proliferative cues are also received from non-myocyte populations such as fibroblasts, which generate several important pro-regenerative extracellular matrix components such as transforming growth factor β (TGFβ), tenascin-C and fibronectin. Platelet-derived growth factor BB isoform (PDGF-BB) and fibroblast growth factor (FGF) are produced by thrombocytes and myocardial cells, respectively, and act on their cognate receptors (PDGFR and FGFR) in the epicardium to promote angiogenesis.
Figure 3
Figure 3
Molecular and cellular mechanisms of cardiac regeneration in neonatal mice. Cardiomyocyte proliferation and angiogenesis are both required for complete regeneration of the neonatal heart following injury. Cardiomyocyte proliferation in the neonatal heart is activated by Yap and restricted by the miR-15 family and Meis1. Macrophages are also recruited to the injury site where they promote angiogenesis.
See this image and copyright information in PMC

References

    1. Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat. Rev. Immunol. 2004;4:553. - PubMed
    1. Ahuja P, Perriard E, Perriard JC, Ehler E. Sequential myofibrillar breakdown accompanies mitotic division of mammalian cardiomyocytes. J. Cell Sci. 2004;117:3295. - PubMed
    1. Allukian M, 3rd, Xu J, Morris M, Caskey R, Dorsett-Martin W, Plappert T, Griswold M, Gorman JH, 3rd, Gorman RC, Liechty KW. Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment. Ann. Thorac. Surg. 2013;96:163. - PMC - PubMed
    1. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN. Macrophages are required for neonatal heart regeneration. J. Clin. Invest. 2014;124:1382. - 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. - PubMed

Publication types