acid-phosphatase and Hypertrophy--Left-Ventricular

Cardiocyte loss during myocardial hypertrophy leads to progressive dysfunction in human hearts with chronic hemodynamic overload. The mechanism for such cell elimination is unknown. We examined lysosomal participation in cardiocytic degradation present in human cardiac biopsies, utilizing electron microscopic cytochemistry (acid phosphatase). Lysosomes were significantly increased in number (t-test, P<0.001) in 50 hemodynamically overloaded hearts (375+/-69, mean+/-s.e.m., per 5,000 microm(2) cardiocytic area; eight controls, 38+/-11). Secondary lysosomes were prominent near degenerative intracellular organelles in both hypertrophic and atrophic cardiocytes. Increased lysosomal and phagocytic activity in the cytoplasm without typical nuclear apoptosis resembled cytoplasmic degradation in developmental programmed cell death described in different tissues. We also demonstrated cardiocytic DNA degradation (in situ nick-end labeling) in autopsy hearts, including 299 nuclei normalized per 10(6) observed nuclei from five concentrically hypertrophied hearts, 1961 nuclei from five eccentrically hypertrophied hearts, and no positive nuclei in five controls. We postulate a chronic self-controlled cytoplasmic proteolysis in cardiocytes, not initially associated with either nuclear degradation or intercellular dehiscence but later possibly accompanied by apoptotic nuclear elimination, and leading to apoptotic cell death.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Cell Death; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; In Situ Nick-End Labeling; Lysosomes; Male; Middle Aged; Myocardium; Ventricular Remodeling