Document Detail

Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis.
MedLine Citation:
PMID:  12615689     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Previously, we demonstrated that activated inducible NO synthase (iNOS)-expressing foam cells in human carotid plaques often produce autofluorescent (per)oxidized lipids (ceroid). Here, we investigate whether intraplaque microvessels can provide foam cells with lipids and trigger macrophage activation.
METHODS AND RESULTS: Microvessels (von Willebrand factor [vWf] immunoreactivity), activated macrophages (iNOS immunoreactivity), and ceroid were systematically mapped in longitudinal sections of 15 human carotid endarterectomy specimens. An unbiased hierarchical cluster analysis classified vascular regions into 2 categories. One type with normal vWf expression and without inflammatory cells was seen, and another type with cuboidal endothelial cells, perivascular vWf deposits, and iNOS and ceroid-containing foam cells was seen in 4 (27%) of 15 plaques. The perivascular foam cells frequently contained platelets (glycoprotein Ibalpha) and erythrocytes (hemoglobin, iron), pointing to microhemorrhage/thrombosis and subsequent phagocytosis. Similar lipid-containing cells, expressing both ceroid and iNOS, were generated in atherosclerosis-free settings by incubating murine J774 macrophages with platelets or oxidized erythrocytes and also in vivo in organizing thrombi in normocholesterolemic rabbits.
CONCLUSIONS: Focal intraplaque microhemorrhages initiate platelet and erythrocyte phagocytosis, leading to iron deposition, macrophage activation, ceroid production, and foam cell formation. Neovascularization, besides supplying plaques with leukocytes and lipoproteins, can thus promote focal plaque expansion when microvessels become thrombotic or rupture prone.
Mark M Kockx; Kristel M Cromheeke; Michiel W M Knaapen; Johan M Bosmans; Guido R Y De Meyer; Arnold G Herman; Hidde Bult
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-01-23
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  23     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-17     Completed Date:  2003-04-11     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  440-6     Citation Subset:  IM    
Division of Pharmacology, University of Antwerp, Belgium.
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MeSH Terms
Arteriosclerosis / complications,  pathology*,  physiopathology*
Cells, Cultured
Ceroid / analysis
Endothelium, Vascular / metabolism
Foam Cells / enzymology
Macrophage Activation*
Neovascularization, Pathologic
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type II
Thrombosis / etiology,  metabolism*
von Willebrand Factor / metabolism
Reg. No./Substance:
0/Ceroid; 0/von Willebrand Factor; EC protein, human; EC Oxide Synthase; EC Oxide Synthase Type II; EC protein, mouse

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