| CD40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization. | |
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MedLine Citation:
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PMID: 18929241 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Our goal was to demonstrate that microparticles (MPs) are the endogenous signal leading to neovessel formation through CD40 ligation in human atherosclerotic plaques. BACKGROUND: Vulnerable atherosclerotic plaques prone to rupture are characterized by an increased number of vasa vasorum and frequent intraplaque hemorrhage. Although inflammatory cytokines, growth factors, or CD40/CD40 ligand (CD40L) are possible candidates, the mechanism of atherosclerotic plaque neovascularization remains unknown. Atherosclerotic plaques contain large amounts of membrane-shed submicron MPs released after cell activation or apoptosis. METHODS: Microparticles were isolated from endarterectomy specimens surgically obtained from 26 patients and characterized by phosphatidylserine exposure and specific markers of cellular origin. RESULTS: Plaque MPs increased both endothelial proliferation assessed by (3)H-thymidine incorporation and cell number and stimulated in vivo angiogenesis in Matrigel (BD Biosciences, San Diego, California) assays performed in wild-type and BalbC/Nude mice, whereas circulating MPs had no effect. Microparticles from symptomatic patients expressed more CD40L and were more potent in inducing endothelial proliferation, when compared with asymptomatic plaque MPs. Most of CD40L+ MPs (93%) isolated from human plaques were of macrophage origin. Microparticle-induced endothelial proliferation was impaired by CD40L or CD40-neutralizing antibodies and abolished after endothelial CD40-ribonucleic acid silencing. In addition, the proangiogenic effect of plaque MPs was abolished in Matrigel assays performed in the presence of CD40L-neutralizing antibodies or in CD40-deficient mice. CONCLUSIONS: These results demonstrate that MPs isolated from human atherosclerotic lesions express CD40L, stimulate endothelial cell proliferation after CD40 ligation, and promote in vivo angiogenesis. Therefore, MPs could represent a major determinant of intraplaque neovascularization and plaque vulnerability. |
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Authors:
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Aurélie S Leroyer; Pierre-Emmanuel Rautou; Jean-Sébastien Silvestre; Yves Castier; Guy Lesèche; Cécile Devue; Micheline Duriez; Ralf P Brandes; Esther Lutgens; Alain Tedgui; Chantal M Boulanger |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American College of Cardiology Volume: 52 ISSN: 1558-3597 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-20 Completed Date: 2008-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
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Languages: eng Pagination: 1302-11 Citation Subset: AIM; IM |
Affiliation:
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Institut National de la Santé et de la Recherche Médicale, Cardiovascular Research Center INSERM Lariboisière, Paris. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Apoptosis / physiology Atherosclerosis / metabolism*, pathology CD40 Ligand / metabolism* Carotid Artery Diseases / metabolism*, pathology, surgery Cell Proliferation Cells, Cultured Culture Media Endarterectomy / methods Endothelium, Vascular / metabolism*, pathology Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Humans Male Neovascularization, Pathologic / metabolism*, pathology Particle Size Reference Values Sensitivity and Specificity |
| Chemical | |
Reg. No./Substance:
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0/Culture Media; 147205-72-9/CD40 Ligand |
| Comments/Corrections | |
Comment In:
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J Am Coll Cardiol. 2008 Oct 14;52(16):1312-3
[PMID:
18929242
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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