Original articles
Cardiovascular
Is the Myofibrillarlytic Myocyte a Forme Fruste Apoptotic Myocyte?

https://doi.org/10.1016/j.athoracsur.2004.09.061Get rights and content

Background

Myofibrillarlytic (MFL) cells are commonly observed in subendocardial myocardium in myocardial infarction. Because ischemic damage to myocytes is also known to induce apoptosis, we evaluated the prevalence of apoptosis in MFL cells in nine ischemic cardiomyopathic hearts explanted during transplantation.

Methods

Myocytes with partial or complete clearing of cytoplasm, observed commonly in the subendocardium, were recognized as MFL cells. Prevalence of apoptosis was defined by TUNEL and ISOL staining and further characterized by immunohistochemical staining for caspase-3, Bcl2, BCL-XL, Bax, proliferating cell nuclear antigen (PCNA), and Ki67.

Results

Of 4131 MFL cells examined, 1305 (32%) possessed nuclei in a given histologic section; 1140 (88%) of the nucleated myocardial cells were TUNEL positive. Of 842 cells with normal appearance, 257 (31%) cells demonstrated nuclei in the given histologic section. TUNEL staining was observed in 5 (1.9%) in these control areas. All MFL cells stained positive for caspase 3. The antiapoptotic proteins, Bcl2 and BCL-XL, demonstrated intense upregulation within and surrounding MFL cells, whereas pro-apoptotic protein Bax expression was only seen at control level. The MFL cells had Ki67 negative and PCNA positive nuclei.

Conclusions

The present study demonstrates that the majority of MFL cells are apoptotic and are associated with upregulation of caspase 3. Simultaneous upregulation of Bcl2 represents a survival effort in these myocytes. This is consistent with the review of the literature that MFL cells are viable, persist in myocardium for long time and may be functionally reversible. Evidence for concurrent apoptosis and survival instinct represent a conceptual paradox and suggests that myocytes undergoing apoptosis should be amenable to reconstitution of function.

Section snippets

Material and Methods

Histologic sections from nine ISCM hearts obtained during transplantation over the past 2 years were reviewed. Section stained by hematoxylin-eosin, which showed large populations of MFL cells in subendocardial layers, were identified. A myofibrillarlytic cell was defined as a myocyte wherein a part or all of the sarcoplasm had been replaced by a clear, intracellular vacuole. The myocytes with only perinuclear clearing were rejected as sectioning artifact. Contiguous sections of the selected

Results

A total of 4131 MFL cells (Fig 1A) were examined; 1305 of these cells possessed nuclei (32%) in the examined sections. Of 1305 MFL cells, 1146 nucleated cells (88%) revealed TUNEL-positive nuclei (Fig 2A). For comparison, 842 normal appearing myocytes were evaluated. Of these, 257 cells (31%) revealed nuclei in the section, merely 5 (1.9%) nuclei were TUNEL positive. No caspase 3 staining was observed in the cytoplasm or nuclei in normal appearing myocytes. On the other hand, all MFL cells

Comment

In the present study almost 90% nuclei of MFL cells in ischemic cardiomyopathic hearts demonstrated apoptosis as detected by TUNEL-based evidence of nuclear fragmentation. Almost all of these cells also demonstrated variable degree of caspase 3 upregulation. Caspase 3 staining was more marked in the cells that had less severe vacuolization. It is logical to presume that activated caspases lead to digestion of contractile proteins to result in cytoplasmic clearance. Peptide sequence analysis of

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