On the nature of cell death during remodeling of hypertrophied human myocardium.

Abstract:

: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.

journal_name

J Mol Cell Cardiol

authors

Yamamoto S,Sawada K,Shimomura H,Kawamura K,James TN

doi

10.1006/jmcc.1999.1064

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

161-75

issue

1

eissn

0022-2828

issn

1095-8584

pii

S0022282899910647

journal_volume

32

pub_type

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