New opportunities for heart disease therapeutics
Apoptosis was first introduced into biology in a seminal paper by a group of pathologists studying cell population regulation (1). In this paper, the authors described a form of cell death marked by its singularity, a unique morphology and resolution without apparent “traces” (e.g., inflammation) in the tissue of origin. These features of cell death were contrasted to various forms of cell death by necrosis, due to noxious stimuli leading to cell membrane disruption, swelling, disintegration, cell-content leakage and local inflammation. Featuring prominently in the apoptotic process are the “apoptotic bodies” (fragments of dense DNA surrounded by an apparently intact plasma membrane), DNA condensation and fragmentation (the latter noted as “ladder” when separated on DNA-gel electrophoresis). The apoptosis phenotype has been later on associated with “programmed cell death” (PCD) described first in the nematode, C. elegance, where genetically specified deletions of cells during development followed a highly timed activation of specific genes (ced-3/4) (2). It is now quite common to use apoptosis and PCD interchangeably; in this review, apoptosis represents the cellular phenotype resulting from activation of genomic programs that lead to DNA damage and cell death. The objectives of this review are: a. to highlight the key evidence on apoptosis in human cardiac myocytes; b. review the key stimuli and signal transduction pathways identified in cardiac myocytes; c. discuss the significance of apoptosis in cardiac function and disease; d. suggest potential novel therapeutic strategies for cardiac diseases based on modulation of selected molecular targets in cardiomyocyte apoptosis.
KeywordsCardiac Myocytes Cardiac Remodel Cardiomyocyte Apoptosis Heart Failure Condition Cardiac Myocyte Apoptosis
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