Possible Mechanism for Disposal of Degenerative Cardiomyocytes in Human Failing Hearts: Phagocytosis by a Neighbour

Figures

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  Figure 1. Light and electron micrographs of the endomyocardial biopsy from Patient 1. (A1 and A2) Cardiomyocytes are separated by a wide interstitium and exhibit severe degenerative changes, including vacuolization and rarefaction of the myofibrils. Haematoxylin and eosin‐stained preparation. Panel (A2) is an expanded view of the area within the square in panel (A1). (B) Masson's trichrome staining shows interstitial, replacement, and endocardial fibrosis (blue area). (C) Electron microscopy revealed cardiomyocytes with scanty myofibrils remaining at the periphery (the so‐called Adria cells). Lp, lipofuscin granules; Mf, myofibrils; N, nucleus. Scale bars: 200 μm in panel (A1), 50 μm in panels (A2) and (B), and 1 μm in panel (C).

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  Figure 2. Electron micrographs obtained from Patient 1 showing a pair of cardiomyocytes consisting of an enclosed cell (asterisk) and an enclosing cell. There is an intercalated disc between them. The enclosed cardiomyocyte appears more degenerative than the enclosing one, with severely disintegrated myofibrils and Z bands broken to pieces. Panels (B) and (C) are expanded views of the areas within the squares in panel (A). ID, intercalated disc; Mf, myofibrils; N, nucleus of the enclosed cardiomyocyte. Scale bars: 1 μm.

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  Figure 3. Electron micrographs from Patient 1 showing a pair of cardiomyocytes consisting of an enclosed cell (asterisk) and an enclosing cell. There is an intercalated disc between them. Apart from the degenerated myofibrils at the periphery, the cytoplasm of the enclosed cardiomyocyte contains almost exclusively glycogen granules. Panels (B) and (C) are expanded views of the areas within the squares in panel (A). GG, glycogen granules; ID, intercalated disc; Mf, myofibrils; Mt, mitochondria. Scale bars: 1 μm.

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  Figure 4. Electron micrographs from Patient 1 showing a pair of cardiomyocytes consisting of an enclosed cell (asterisk) and an enclosing cell at a degenerative stage. The enclosed cell is nearly indistinguishable from a phagocytized cell or giant autophagic vacuole within the enclosing cardiomyocyte. The intercalated disc is dilated to look like a simple double membrane, and desmosomes at the periphery of the enclosed cardiomyocyte have disappeared such that the structures are now unilateral (white arrows). Panels (B) and (C) are expanded views of the areas within the squares in panel (A). ID, intercalated disc; Mf, myofibrils. Scale bars: 1 μm.

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  Figure 5. Electron micrographs from Patient 1 showing a pair of cardiomyocytes consisting of an enclosed cell (asterisk) and an enclosing cell at a degenerative stage. Many desmosomes on the intercalated disc have become unilateral (white arrows). The border between the cardiomyocytes is sometimes disrupted (white arrowheads), and the cellular contents appear to be shared between the two cells. Panel (B) is an expanded view of the area within the square in panel (A). ID, intercalated disc. Scale bars: 1 μm.

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  Figure 6. Electron micrographs obtained from Patient 2 showing a pair of cardiomyocytes closely contacting each other. The nearly intact cell looks as if it is enclosing a severely degenerated cell (asterisk) containing scanty myofibrils and structures reminiscent of Z bands. The intercalated disc between the two cardiomyocytes possesses incomplete or unilateral desmosomes in some areas (panel (B)), and it completely lacks of desmosomes in other areas (panel (C)). Panels (B) and (C) are expanded views of the areas within the squares in panel (A). GG, glycogen granules; ID, intercalated disc; Lp, lipofuscin; Mf, myofibrils; Mt, mitochondria; N, nucleus of the enclosing cardiomyocyte. Scale bars: 1 μm.

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  Figure 7. Hypothesized mechanism for disposal of degenerative/dead cardiomyocytes in heart failure deduced from the present cases. (A) A severely degenerative/dead cardiomyocyte (asterisks) is enclosed by a neighbouring one (left side). (B) The intercalated disc then degenerates and becomes dilated (dID), while desmosomes at the periphery of the enclosed cardiomyocyte disappear such that they become unilateral (uD) (middle panels). (C) The intercalated disc ultimately fades away, and the cellular contents are shared between the two cells (right panels). D, desmosome; dID, degenerated intercalated disc; dMf, degenerated myofibrils; dZB, degenerated Z band; ID, intercalated disc; Mf, myofibrils; uD, unilateral desmosome.