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01 July 2005 : Case report  

Is restoring regenerative potential a way to prevent anthracycline cardiotoxicity? A hypothesis.

Arnold Koller, Christian Haid

Med Sci Monit 2005; 11(7): HY12-23 :: ID: 16857


Anthracycline-induced cardiotoxic effects are a serious problem among young patients who survive childhood cancer and there is an urgent need to avoid such effects. It is generally accepted that the only effective way to do this is to prevent cardiac injury during chemotherapy. There are several possible ways to do this, though questions remain. Evidence suggests the existence of a resident population of self-renewing cardiac stem cells capable of contributing to heart repair. Cardiac stem cells have an intrinsically poor regenerative response to heart injury. However, recent results point to ways to enhance the formation of cardiac precursor cells necessary for regeneration after injury. Moreover, the results of a recent study demonstrated that activation of the Notch signaling pathway, well characterized for its role in myogenesis and tissue formation during embryogenesis, restores impaired regenerative potential of skeletal muscle by activating resident precursor cells (satellite cells), which have a markedly impaired propensity to proliferate and to produce the myoblasts necessary for muscle regeneration. Based on these findings, and because the mechanisms behind the cardiotoxic effects of anthracyclines are not fully understood and current ways to avoid anthracycline-induced cardiotoxic effects have limitations, we hypothesize herein that an attractive way to avoid these effects may be to promote repair and regeneration, as opposed to prevent injury (e.g. by dexrazoxane).

Keywords: Anthracyclines - adverse effects, Anthracyclines - therapeutic use, Heart Diseases - chemically induced, Heart Diseases - prevention & control, Myoblasts, Cardiac - drug effects, Myoblasts, Cardiac - metabolism, Myoblasts, Cardiac - physiology, Anthracyclines - therapeutic use, Antineoplastic Agents - therapeutic use, Cell Differentiation, Heart Diseases - prevention & control, Membrane Proteins - metabolism, Myoblasts, Cardiac - physiology, Myocardium - pathology, Receptors, Notch, Regeneration, Stem Cells - physiology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750