Publication
Title
Cell death-mediated cleavage of the attraction signal p43 in human atherosclerosis: implications for plaque destabilization
Author
Abstract
Objective-: Apoptosis is a key feature of advanced atherosclerotic plaques. Attraction signals such as p43 released from apoptotic cells play a crucial role in the timely removal of the apoptotic remnants by recruiting fresh phagocytes. Here, we sought to determine whether p43 may link apoptosis to inflammation and plaque progression. Methods and Results-: RT-PCR and immunohistochemistry showed that p43 was abundantly expressed in human plaques compared with nonatherosclerotic mammary arteries and colocalized with splicing factor SC-35. Cell culture experiments indicated that p43 expression was associated with enhanced protein translation. On initiation of apoptosis or necrosis, p43 was cleaved by calpains and released as truncated protein p43(ARF). Processing of p43 into endothelial monocyte activating polypeptide II was not observed. Full-length p43, but not p43(ARF) or endothelial monocyte activating polypeptide II, activated THP1 monocytes (upregulation of tumor necrosis factor [alpha], interleukin 1[beta], interleukin 8, MIP1[alpha], MIP1[beta], MIP2[alpha]) and endothelial cells (enhanced synthesis of E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tissue factor). The chemotactic activity of p43 or fragments thereof was poor compared with ATP. Treatment of smooth muscle cells with p43 did not induce cell death. Conclusion-: p43 is cleaved during apoptosis by calpains and released as a truncated protein that is harmless for the structure of the plaque.
Language
English
Source (journal)
Arteriosclerosis, thrombosis, and vascular biology / American Heart Association. - Dallas, Tex., 1995, currens
Publication
Dallas, Tex. : 2010
ISSN
1079-5642
1524-4636 [online]
Volume/pages
30:7(2010), p. 1415-1422
ISI
000278856600019
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 18.05.2010
Last edited 26.06.2017
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