Apoptotic death of inflammatory cells in human atheroma

Citation
W. Li et al., Apoptotic death of inflammatory cells in human atheroma, ART THROM V, 21(7), 2001, pp. 1124-1130
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
21
Issue
7
Year of publication
2001
Pages
1124 - 1130
Database
ISI
SICI code
1079-5642(200107)21:7<1124:ADOICI>2.0.ZU;2-9
Abstract
Although the accumulation of cholesterol and other lipidic material is unqu estionably important in atherogenesis, the reasons why this material progre ssively accumulates, rather than being effectively cleared by phagocytic ce lls such as macrophages, are not completely understood. We hypothesize that atheromatous lesions may represent "death zones" that contain toxic materi als such as oxysterols and in which monocytes/macrophages become dysfunctio nal and apoptotic. Indeed, cathepsins B and L, normally confined to the lys osomal compartment, are present in the cytoplasm and nuclei of apoptotic (c aspase-3-positive) macrophages within human atheroma. The possible involvem ent of oxysterols is suggested by experiments in which cultured U937 and TH P-1 cells exposed to 7-oxysterols similarly undergo marked lysosomal destab ilization, caspase-3 activation, and apoptosis. Like macrophages within ath eroma, intralysosomal cathepsins B and L are normally present in the cytopl asm and nuclei of these oxysterol-exposed cells. Lysosomal destabilization, cathepsin release, and apoptosis may be causally related, because inhibito rs of cathepsins B and L suppress oxysterol-induced apoptosis. Thus, toxic materials such as 7-oxysterols in atheroma may impair the clearance of chol esterol and other lipidic material by fostering the apoptotic death of phag ocytic cells, thereby contributing to further development of atheroscleroti c lesions.