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

被引:71
作者
Yamamoto, S
Sawada, K
Shimomura, H
Kawamura, K
James, TN
机构
[1] Univ Texas, Med Branch, Dept Med, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA
[3] Osaka Med Coll, Osaka, Japan
关键词
apoptosis; acid phosphatase; phagocytosis; biopsy; cytoplasm;
D O I
10.1006/jmcc.1999.1064
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 5000 mu m(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 live 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. (C) 2000 Academic Press.
引用
收藏
页码:161 / 175
页数:15
相关论文
共 76 条
[1]   Enhanced Gαq signaling:: A common pathway mediates cardiac hypertrophy and apoptotic heart failure [J].
Adams, JW ;
Sakata, Y ;
Davis, MG ;
Sah, VP ;
Wang, YB ;
Liggett, SB ;
Chien, KR ;
Brown, JH ;
Dorn, GW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (17) :10140-10145
[2]  
Alberts B, 1994, MOL BIOL CELL, P599
[3]   HISTOCHEMICAL METHODS FOR ACID PHOSPHATASE USING HEXAZONIUM PARAROSANILIN AS COUPLER [J].
BARKA, T ;
ANDERSON, PJ .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1962, 10 (06) :741-&
[4]  
BELCH JJF, 1991, BRIT HEART J, V65, P245
[5]   Stress (heat shock) proteins - Molecular chaperones in cardiovascular biology and disease [J].
Benjamin, IJ ;
McMillan, DR .
CIRCULATION RESEARCH, 1998, 83 (02) :117-132
[6]  
BREISCH EA, 1982, CELL TISSUE RES, V223, P615
[7]   STRETCH-INDUCED PROGRAMMED MYOCYTE CELL-DEATH [J].
CHENG, W ;
LI, BS ;
KAJSTURA, J ;
LI, P ;
WOLIN, MS ;
SONNENBLICK, EH ;
HINTZE, TH ;
OLIVETTI, G ;
ANVERSA, P .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (05) :2247-2259
[8]  
CIECHANOVER A, 1994, BIOL CHEM H-S, V375, P565
[9]   DEVELOPMENTAL CELL-DEATH - MORPHOLOGICAL DIVERSITY AND MULTIPLE MECHANISMS [J].
CLARKE, PGH .
ANATOMY AND EMBRYOLOGY, 1990, 181 (03) :195-213
[10]   Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the β-adrenergic pathway [J].
Communal, C ;
Singh, K ;
Pimentel, DR ;
Colucci, WS .
CIRCULATION, 1998, 98 (13) :1329-1334