Heart disease: Death-defying plaque cells

Abstract

Dead cells are usually removed through their ingestion and destruction by other cells. A study of plaque deposits in arteries shows that dying cells in plaques display a ‘don’t-eat-me’ signal that blocks their removal.

Figure 1. Defective removal of dead cells can contribute to clinically dangerous atherosclerotic plaques

a, Many clinically dangerous plaques contain a structure called the necrotic core, characterized by inflammation and necrotic cell death. In atherosclerosis, if the fibrous cap covering the plaque ruptures or erodes, release of material from the necrotic core can trigger platelet aggregation (known as a thrombus) and arterial blockage, which may result in heart attack or stroke. Understanding how plaques develop to a necrotic state is a key question. b, Plaque cells undergo a non-inflammatory type of cell death called apoptosis. In asymptomatic non-necrotic plaques, rapid removal of apoptotic cells by engulfing cells — a process known as efferocytosis — prevents necrosis. c, Kojima et al. found that the inflammatory conditions of advanced atherosclerosis lead to persistent expression of the protein marker CD47 on plaque cells through the inflammatory-signalling mediator NF-κB. When these cells become apoptotic, CD47 sends a signal through the SIRPα receptor on the engulfing cell to block engulfment. The unengulfed cells undergo a type of cell death called secondary necrosis, leading to the release of inflammatory molecules and the formation of necrotic cores from the cell debris.