Possible mechanism for disposal of degenerative cardiomyocytes in human failing hearts: phagocytosis by a neighbour

The index case was a 51‐year‐old woman suffering from doxorubicin cardiomyopathy. In her endomyocardial biopsy specimen, we observed under electron microscopy six scenes in which degenerative cardiomyocytes were engulfed by neighbouring cardiomyocytes. The enclosed cardiomyocytes appeared more degenerative than the enclosing ones in every pair: the myofibrils were more severely damaged. At more degenerative stages, some desmosomes of the intercalated discs on the enclosed cardiomyocyte had disappeared. The membranes between the cardiomyocytes were occasionally disrupted, and there appeared to be sharing of cellular contents between the cells. One pair of such a phagocytosis‐like figure was observed in one case with 5‐fluorouracil cardiomyopathy (a 68‐year‐old man) among eight other chemotherapy‐induced cardiomyopathies but none among 30 non‐drug‐induced dilated cardiomyopathies. The findings suggest a mechanism for disposal of degenerative cardiomyocytes in human failing hearts: phagocytosis by a neighbour, although alternative interpretations remain (e.g. giant autophagic vacuoles or two cardiomyocytes with degenerative intercalated discs).

[1]  G. Takemura,et al.  Ultrastructural aspects of vacuolar degeneration of cardiomyocytes in human endomyocardial biopsies. , 2017, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[2]  C. Vecchione,et al.  A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling , 2017, Oxidative medicine and cellular longevity.

[3]  V. Urmaliya,et al.  A multidimensional sight on cardiac failure: uncovered from structural to molecular level , 2017, Heart Failure Reviews.

[4]  E. Passante,et al.  Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited , 2016, Journal of Molecular Medicine.

[5]  F. Spinale,et al.  Changes in the myocardial interstitium and contribution to the progression of heart failure. , 2012, Heart failure clinics.

[6]  S. Nagata,et al.  Autoimmunity and the Clearance of Dead Cells , 2010, Cell.

[7]  J. Dalzell,et al.  The spectrum of 5-fluorouracil cardiotoxicity , 2009, Anti-cancer drugs.

[8]  G. Takemura,et al.  Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. , 2007, Progress in cardiovascular diseases.

[9]  L. Gianni,et al.  Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity , 2004, Pharmacological Reviews.

[10]  M. Arai,et al.  Characterization of ultrastructure and its relation with DNA fragmentation in Fas‐induced apoptosis of cultured cardiac myocytes , 2001, The Journal of pathology.

[11]  V. Ferrans,et al.  Doxorubicin-induced apoptosis in spontaneously hypertensive rats: differential effects in heart, kidney and intestine, and inhibition by ICRF-187. , 1996, Journal of molecular and cellular cardiology.

[12]  D. Keefe,et al.  Clinical Cardiotoxicity of 5‐Fluorouracil , 1993, Journal of clinical pharmacology.

[13]  J. Almenarez,et al.  Lethal Cardiac Toxicity after Cisplatin and 5‐Fluorouracil Chemotherapy: Report of a Case with Necropsy Study , 1989, American journal of clinical oncology.

[14]  I. Mccoll,et al.  5-FLUOROURACIL AND ANGINA , 1975, The Lancet.