zombie

Limits Activated: Humans, Review

1. Cardiol Clin. 2001 Feb;19(1):113-26.

Apoptosis and the systolic dysfunction in congestive heart failure. Story of
apoptosis interruptus and zombie myocytes.

Narula J, Arbustini E, Chandrashekhar Y, Schwaiger M.

Division of Cardiology, Heart Failure and Transplantation Center, MCP-Hahnemann
University School of Medicine, Philadelphia, Pennsylvania 19102-1192, USA.
jagat.narula@drexel.edu

Although previously it was believed that apoptosis could not occur in the
terminally differentiated tissue, such as adult heart muscle cells, recent
studies in endomyocardial biopsies from patients with dilated cardiomyopathy and 
in explanted hearts from patients with end-stage heart failure undergoing cardiac
transplantation have demonstrated histologic evidence of apoptosis. Whereas
neurohormonal activation during heart failure leads to compensatory hemodynamic
alterations, coupled with ventricular dilatation, it induces transcription
factors and myocyte hypertrophy. Persistent growth stimulation in terminally
differentiated cells may lead paradoxically to apoptotic cell death. The
apoptosis in cardiomyopathic hearts is associated with cytochrome c release from 
mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3.
Although the caspases are duly processed, the fragmentation of the nuclear
proteins (including DNA) is completed less frequently, and only a variable degree
of fragmentation of cytoplasmic proteins (including contractile proteins) is
observed. It is hypothesized that release of cytochrome c from mitochondria
should interfere with energy production and lead to functional impairment and
variable loss of contractile proteins in a living heart muscle cell should
contribute to systolic dysfunction. Because a nuclear blueprint is retained,
however, the dysfunctional cell may continue to exist and in favorable
conditions, such as with LVAD support, the apoptotic process may subside.
Potential feasibility of reversal of heart failure should renew efforts to
develop more targeted pharmaceutical intervention within the apoptotic cascade
and allow newer paradigm for the management of heart failure.

PMID: 11787805 [PubMed - indexed for MEDLINE]