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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1694.)
© 2008 American Heart Association, Inc.

Brief Reviews

Death Receptors and Their Ligands in Atherosclerosis

Mary M. Kavurma; Nicole Y. Tan; Martin R. Bennett

From the Centre for Vascular Research (M.M.K., N.Y.T.), The University of New South Wales, Australia; and the Division of Cardiovascular Medicine (M.R.B.), University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.

Correspondence to Dr Mary M. Kavurma, The Centre for Vascular Research, The University of New South Wales, Sydney NSW 2052, Australia. E-mail m.kavurma{at}unsw.edu.au

Atherosclerosis is characterized by the accumulation of a fibro-fatty plaque consisting of immune cells, vascular smooth muscle cells (VSMCs), vascular endothelial cells (ECs), and extracellular matrix, surrounding a lipid-rich core. The complexity of atherosclerosis is highlighted by the multifaceted effects that apoptosis and proliferation of specific cell types can have on vessels at different stages of the disease. Death receptors are membrane-bound protein complexes that on binding their cognate ligand, activate an intracellular signaling cascade that results in apoptosis. More recently, signaling from these receptors has been shown to activate multiple other processes, including cell proliferation. This review summarizes our current understanding of signaling events after death receptor activation and the role of death receptors and their ligands in atherosclerosis.

On binding to their ligands, death receptors transmit apoptotic signals leading to irreversible programmed cell death. Recent studies also implicate death receptors in survival/activation signals, and consequently their role in atherosclerosis is unclear. This review encapsulates our recent understanding of death receptor signaling in atherosclerosis and related disorders.

Key Words: apoptosis • TNF/TNFR signalling • proliferation • atherosclerosis