Myocardial cell death in fibrillating and dilated human right atria
| Autor: | Michel Aubier, John C. Reed, Maryla Krajewska, Stanislaw Krajewski, Catherine Rucker-Martin, Jean-Jacques Mercadier, Michèle Heimburger, Thierry Folliguet, Stéphane N. Hatem, Christine Aimé-Sempé |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male medicine.medical_specialty Programmed cell death Blotting Western Apoptosis Caspase 3 Pathogenesis Internal medicine Atrial Fibrillation In Situ Nick-End Labeling medicine Humans Myocyte Aged Aged 80 and over Electrophoresis Agar Gel TUNEL assay business.industry Myocardium Atrial fibrillation Middle Aged Atrial Function medicine.disease Immunohistochemistry Blot Ki-67 Antigen Endocrinology Caspases cardiovascular system Female Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of the American College of Cardiology. 34:1577-1586 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/s0735-1097(99)00382-4 |
| Popis: | OBJECTIVES The aim of the present study was to determine if myocytes can die by apoptosis in fibrillating and dilated human atria. BACKGROUND The cellular remodeling that occurs during atrial fibrillation (AF) may reflect a degree of dedifferentiation of the atrial myocardium, a process that may be reversible. METHODS We examined human right atrial myocardium specimens (n = 50) for the presence of apoptotic myocytes. We used immunohistochemical and Western blotting analysis to examine the expression of a final effector of programmed cell death, caspase-3 (CASP-3) and of regulatory proteins from the BCL-2 family. RESULTS Sections from atria in AF contained a high percentage of large myocytes with a disrupted sarcomeric apparatus replaced by glycogen granules (64.4 ± 6.3% vs. 12.2 ± 5.8%). These abnormal myocytes, which also predominated in atria from hearts with decreased left ventricular ejection fraction (42.3 ± 10.1%), contained large nuclei, most of which were TUNEL positive, indicating a degree of DNA breakage. None of these abnormal myocytes expressed the proliferative antigen Ki-67. A small percentage of the enlarged nuclei (4.2 ± 0.8%) contained condensed chromatin and were strongly TUNEL positive. Both the pro- and activated forms of CASP-3 were detected in diseased myocardial samples, which also showed stronger CASP-3 expression than controls. Expression of the antiapoptotic BCL-2 protein was decreased in diseased atria, whereas that of the proapoptotic BAX protein remained unchanged. CONCLUSIONS In fibrillating and dilated atria, apoptotic death of myocytes with myolysis contributes to cellular remodeling, which may not be entirely reversible. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|