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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:895.)
© 2005 American Heart Association, Inc.

Brief Reviews

Role of Caspases in Death and Survival of the Plaque Macrophage

Thomas Q. Nhan; W. Conrad Liles; Stephen M. Schwartz

From the Departments of Pathology (T.Q.N., W.C.L., S.M.S.) and Medicine (W.C.L.), University of Washington, Seattle, Wash.

Correspondence to Stephen M. Schwartz, Department of Pathology, University of Washington, 815 Mercer St, Room 421, Seattle, WA 98195-4717. E-mail steves{at}u.washington.edu

This review considers the role of macrophage cell death in formation of the necrotic core and in plaque progression, and lists many of the possible mediators of macrophage cell death. Among these, perhaps the most cited toxic agent is oxidized low-density lipoprotein (oxLDL). Whereas oxLDL can kill macrophage, and whereas the form of death is morphologically apoptotic, caspase inhibitors appear to be ineffective in preventing death. This finding is consistent with recent literature showing how the canonical caspase pathways are used for physiological cellular functions other than cell death. Plaque macrophages appear to be among the cells with this nonapoptotic signaling function for activated caspases. In many of the other cell types, caspase activation appears to play a critical role in cell differentiation. We discuss possible functions of plaque macrophage using the nondeath caspase pathway. Recent literature shows that physiological and developmental functions of many cell types require active caspases without progressing to cell death. We discuss the role of macrophage cell death in plaque progression, possible mediators of macrophage cell death, and the possible functions of plaque macrophage using the nondeath caspase pathway.

Recent literature shows that physiological and developmental functions of many cell types require active caspases without progressing to cell death. We discuss the role of macrophage cell death in plaque progression, possible mediators of macrophage cell death, and the possible functions of plaque macrophage using the nondeath caspase pathway.

Key Words: apoptosis • caspase • death receptors • monocyte/macrophage • plaque rupture

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