Document Detail


Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure.
MedLine Citation:
PMID:  12958145     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronological myocardial aging is viewed as the inevitable effect of time on the functional reserve of the heart. Cardiac failure in elderly patients is commonly interpreted as an idiopathic or secondary myopathy superimposed on the old heart independently from the aging process. Thus, aged diseased hearts were studied to determine whether cell regeneration was disproportionate to the accumulation of old dying cells, leading to cardiac decompensation. Endomyocardial biopsies from 19 old patients with a dilated myopathy were compared with specimens from 7 individuals of similar age and normal ventricular function. Ten patients with idiopathic dilated cardiomyopathy were also analyzed to detect differences with aged diseased hearts. Senescent cells were identified by the expression of the cell cycle inhibitor p16INK4a and cell death by hairpin 1 and 2. Replication of primitive cells and myocytes was assessed by MCM5 labeling, myocyte mitotic index, and telomerase function. Aged diseased hearts had moderate hypertrophy and dilation, accumulation of p16INK4a positive primitive cells and myocytes, and no structural damage. Cell death markedly increased and occurred only in cells expressing p16INK4a that had significant telomeric shortening. Cell multiplication, mitotic index and telomerase increased but did not compensate for cell death or prevented telomeric shortening. Idiopathic dilated cardiomyopathy had severe hypertrophy and dilation, tissue injury, and minimal level of p16INK4a labeling. In conclusion, telomere erosion, cellular senescence, and death characterize aged diseased hearts and the development of cardiac failure in humans.
Authors:
Cristina Chimenti; Jan Kajstura; Daniele Torella; Konrad Urbanek; Hubert Heleniak; Claudia Colussi; Franca Di Meglio; Bernardo Nadal-Ginard; Andrea Frustaci; Annarosa Leri; Attilio Maseri; Piero Anversa
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-09-04
Journal Detail:
Title:  Circulation research     Volume:  93     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-03     Completed Date:  2003-10-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  604-13     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Institute, Department of Medicine, New York Medical College, Vosburgh Pavilion, Room 302, Valhalla, NY 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Biopsy
Cardiomyopathy, Dilated / pathology
Cell Aging*
Cell Cycle Proteins / metabolism
Cell Death
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
DNA-Binding Proteins
Female
Heart Failure / pathology*
Humans
Male
Microscopy, Confocal
Mitotic Index
Myocardium / metabolism,  pathology*
Myocytes, Cardiac / metabolism,  pathology*
Schizosaccharomyces pombe Proteins
Telomerase / metabolism
Grant Support
ID/Acronym/Agency:
AG-023071/AG/NIA NIH HHS; AG-15756/AG/NIA NIH HHS; AG-17042/AG/NIA NIH HHS; HL-38132/HL/NHLBI NIH HHS; HL-65573/HL/NHLBI NIH HHS; HL-65577/HL/NHLBI NIH HHS; HL-66923/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/DNA-Binding Proteins; 0/Schizosaccharomyces pombe Proteins; 0/mcm5 protein, S pombe; EC 2.7.7.49/Telomerase

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