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APOPTOSIS IN THE CARDIOVASCULAR SYSTEM
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  1. Martin R Bennett
  1. Correspondence to:
    Professor Martin R Bennett, Box 110, Unit of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK;
    mrb{at}mole.bio.cam.ac.uk

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Apoptosis, or programmed cell death, is a process through which multicellular organisms dispose of cells efficiently. Much has been discovered about the molecular control of apoptosis since its initial description as a series of morphological events.1 Apoptosis defines a type of cell death distinct from the more conventional necrotic death, seen classically in myocardial infarction, on the basis of characteristic morphological features (table 1, fig 1). Although these descriptions and distinctions are useful, there is a great deal of overlap between apoptosis and necrosis in morphological features and biochemical events. Indeed, apoptosis is frequently followed by secondary necrosis of cells, especially if there is failure of clearance or ingestion of apoptotic bodies.

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Table 1

Characteristic features of apoptosis versus necrosis

Figure 1

Electron microscopic appearances of a human vascular smooth muscle cell (VSMC) undergoing apoptosis in culture. (A) Normal appearance of a human VSMC. VSMC also contains an apoptotic body (arrow). (B) Peripheral condensation of nuclear chromatin. (C) Intense membrane blebbing and vesicle formation in apoptosis, with condensation of the nuclear chromatin into clumps. (D) An apoptotic body, the end product of apoptosis.

DETECTION OF APOPTOSIS

Apoptotic cells undergo a characteristic cascade of biochemical events (see Regulation of apoptosis), many of which are useful in detecting apoptotic cells. In particular, apoptotic cells expose specific membrane phospholipids that can be detected with labelled marker proteins (for example, phosphatidylserine detected with fluorescently labelled annexin V) and cleave their DNA into specific fragments that are the basis for the enzyme linked assays to detect fragmented DNA (for example, terminal UTP nick end labelling, or TUNEL). Biochemical signalling during apoptosis, such as activation or cleavage of specific caspase enzymes (see below) can also be used on both cells and tissue samples. While helpful, the gold standard for detecting apoptosis is still based on morphology at both the light and particularly …

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