Phagocytosis of dying cells in the pathogenesis of atherosclerosis

Abstract

Atherosclerosis is a progressive inflammatory disease characterized by the formation of atheromatous plaques in the intima of medium- and large-sized arteries. A large body of evidence indicates that apoptosis is a prominent feature of advanced plaques. The phagocytic clearance of apoptotic cells by macrophages in these lesions is severely impaired, which is at least partly attributed to oxidative stress and cytoplasmic saturation with indigestible material. The consequences of this defect are likely to be substantial because it promotes three main processes-inflammation, necrosis and thrombosis-that are thought to play an important role in plaque disruption and its acute clinical consequences such as myocardial infarction and stroke. Moreover, the lack of lesional phagocytes to safely clear apoptotic cells undermines the relevance of recent therapeutic approaches to stabilize vulnerable plaques via selective induction of macrophage death. To limit the detrimental effects of defective phagocytic clearance of apoptotic cells, suppression of apoptosis in atherosclerotic plaques is not recommended because reduced levels of macrophage apoptosis promotes plaque development. A more promising approach would be to therapeutically enhance selective phagocytosis of apoptotic cells, on condition that this intervention does not alter the uptake of other plaque components such as lipoproteins, erythrocytes or platelets, an event that is considered to be pro-atherogenic. © 2009 Springer Netherlands.