Necrotic and apoptotic myocyte cell death in the aging heart of
fischer 344 rats.
Kajstura, Jan, Wei Cheng, Ranganathan Sarangarajan, Peng Li, Baosheng
Li, James A. Nitahara, Suzanne Chapnick, Krzysztof Reiss, Giorgio
Olivetti, and Piero Anversa.
Department of Medicine and **Pathology, New York Medical College,
Valhalla, New York 10595
APStracts 3:0052H, 1996.
To determine the effects of aging on myocyte cell death, Fischer 344
rats at 3, 7, 12, 16 and 24 months of age were injected with myosin
monoclonal antibody for the localization and quantification of
necrotic myocyte cell death in the left ventricle, interventricular
septum and right ventricle. Conversely, the presence of DNA strand
breaks in myocyte nuclei, indicative of programmed cell death, was
evaluated by the terminal deoxynucleotidyl transferase assay and
confirmed by DNA laddering. Myocyte necrosis which involved nearly
1,000 myocytes in the left ventricular free wall at 3 months,
progressively increased with aging reaching a value of 13,600 at 24
months. Corresponding values in the interventricular septum were 300
and 9,400. In the right ventricle, there was 270 necrotic myocytes at
3 months and 9,000 at 24 months. Programmed myocyte cell death was
restricted to the left ventricular free wall and included 140 cells
at 3 months. This form of myocyte cell death increased at the
subsequent age intervals, resulting in the involvement of 874 cells
at 24 months. The combination of necrosis and apoptosis in the left
ventricular free wall was associated with 1,150 cells dying at 3
months, and 14,500 at 24 months. In conclusion, myocyte cell death,
apoptotic and necrotic in nature, constitutes an important
determinant of the aging process, possibly mediating the occurrence
of ventricular dysfunction and failure in the old heart.
Received 10 November 1995; accepted in final form 22 January
1996.
APS Manuscript Number H1058-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96