densation and the formation of membrane-bound Since the original morphological description of apovesicles called apoptotic bodies. These are phagoptosis many molecular mechanisms that characterise cytosed by adjacent cells and macrophages without the apoptotic pathway have been identified. Apoptosis inducing an inflammatory response. In contrast, necis controlled by a well-ordered cascade of cellular rotic cells sustain membrane damage leading to the events that may be divided into four stages (initiation, release of pro-inflammatory intracellular contents. control/execution, structural/morphological alApoptosis although recognised to be fundamentally teration and phagocytic recognition) (Fig. 1). Initiation important in development also occurs in normal of apoptosis may occur following the binding of death physiological circumstances. Apoptotic vascular promoting factors (e.g. Tumour Necrosis Factor (TNF) smooth muscle cells (VSMCs) have been identified and Fas Ligand) to cell surface TNF and Fas death during the physiological regression and closure of receptors or by a withdrawal of survival factors (e.g. the human ductus arteriosus before birth. Similarly, reduced insulin-like growth factor, loss of cell–cell apoptotic VSMCs and endothelial cells are present in and cell–matrix contact) acting via the mitochondria. umbilical veins and arteries following the significant Alternatively apoptosis may be initiated by ionising haemodynamic changes that occur during birth. Such radiation or chemotherapeutic agents acting directly apoptosis appears to be triggered by a reduction in on DNA. blood flow. Further support comes from experimental The control and execution stage of apoptosis is studies using immature rabbits which demonstrate dependent on the sequential activation of a group of that reducing flow in the common carotid artery, by cysteine proteases referred to as caspases. Activation ligating the external carotid, results in both VSMC and of caspase-8 occurs following binding of the cell surface endothelial cell apoptosis. The normal blood vessel death-receptors (TNF and Fas). Caspase-9 is activated wall is characterised by a low endothelial cell turnover by cytochrome C released from mitochondria stimwith a variety of mechanisms affording protection ulated by the withdrawal of survival factors. Both against apoptosis. Indeed, recent data indicate that caspase-8 and 9 can activate the final executioner, apoptosis may be important in the pathophysiology caspase-3, which in turn causes the irreversible fragof vascular disease. A better understanding of this mentation and degradation of DNA.