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Heart regeneration in adult MRL mice

John M. Leferovich, Khamilia Bedelbaeva, Stefan Samulewicz, Xiang-Ming Zhang, Donna Zwas, Edward B. Lankford, and Ellen Heber-Katz
PNAS August 14, 2001 98 (17) 9830-9835; https://doi.org/10.1073/pnas.181329398
John M. Leferovich
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Khamilia Bedelbaeva
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Stefan Samulewicz
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Xiang-Ming Zhang
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Donna Zwas
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Edward B. Lankford
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Ellen Heber-Katz
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  1. Communicated by Hilary Koprowski, Thomas Jefferson University, Philadelphia, PA (received for review April 20, 2001)

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Abstract

The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10–20% for the MRL compared with 1–3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.

Footnotes

    • ↵§ To whom reprint requests should be addressed. E-mail: heberkatz{at}mail.wistar.upenn.edu.

  • Abbreviations

    RV,
    right ventricle;
    LV,
    left ventricle;
    RT,
    reverse transcription;
    EDD,
    end diastolic dimension
    • Received April 20, 2001.
    • Accepted June 29, 2001.
    • Copyright © 2001, The National Academy of Sciences
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    Heart regeneration in adult MRL mice
    John M. Leferovich, Khamilia Bedelbaeva, Stefan Samulewicz, Xiang-Ming Zhang, Donna Zwas, Edward B. Lankford, Ellen Heber-Katz
    Proceedings of the National Academy of Sciences Aug 2001, 98 (17) 9830-9835; DOI: 10.1073/pnas.181329398

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    Heart regeneration in adult MRL mice
    John M. Leferovich, Khamilia Bedelbaeva, Stefan Samulewicz, Xiang-Ming Zhang, Donna Zwas, Edward B. Lankford, Ellen Heber-Katz
    Proceedings of the National Academy of Sciences Aug 2001, 98 (17) 9830-9835; DOI: 10.1073/pnas.181329398
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