Autophagic degeneration as a possible mechanism of myocardial cell death in dilated cardiomyopathy

In failing hearts, cardiomyocytes degenerate and interstitial fibrosis, whi ch indicates cardiomyocyte loss, becomes more prominent in the myocardium. However, the precise mechanism of cardiomyocyte degeneration that leads to cell death is still unclear, although it is presumed that lysosomal functio n and autophagy play an important role because lysosomal activity increases under stress such as hypoxia. Myocardium that had been resected during par tial left ventriculectomy performed in patients with dilated cardiomyopathy (DCM) was examined. Under light microscopy, some cardiomyocytes had a mark ed scarcity of myofibrils and had prominent cytoplasmic vacuolization. Atro phic and degenerated cardiomyocytes were often observed adjacent to replace ment fibrotic tissue. Immunohistochemistry showed positivity for lysosome-a ssociated membrane protein and a lysosomal catheptic enzyme in vacuoles of various sizes in the cardiomyocytes and these lysosomal markers were marked ly increased in atrophic and degenerated cardiomyocytes. Electron microscop y revealed that degenerated cardiomyocytes had many vacuoles containing int racellular organelles, such as mitochondria, and were considered to be auto phagic vacuoles. In DCM hearts, autophagy appeared to be associated not onl y with degradation of damaged intracellular organelles but also with progre ssive destruction of cardiomyocytes. It is possible that autophagic degener ation is one of the mechanisms of myocardial cell death.