Document Detail

Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis.
MedLine Citation:
PMID:  20956207     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis. Previous data indicate important roles for monocytes and T lymphocytes in lesion formation, whereas the contribution of neutrophils remains to be firmly established. Here, we investigate the effect of hypercholesterolemia on peripheral neutrophil counts, neutrophil recruitment to atherosclerotic lesions, and the importance of neutrophils in atherosclerotic lesion formation in Apoe(-/-) mice.
METHODS AND RESULTS: Hypercholesterolemia induces neutrophilia, which was attributable to enhanced granulopoiesis and enhanced mobilization from the bone marrow. The degree of hypercholesterolemia-induced neutrophilia was positively correlated with the extent of early atherosclerotic lesion formation. In turn, neutropenic mice display reduced plaque sizes at early but not late stages of atherosclerotic lesion formation. Flow cytometry of enzymatically digested aortas further shows altered cellular plaque composition in neutropenic mice with reduced numbers of inflammatory monocytes and macrophages. Aortic neutrophil infiltration peaks 4 weeks after the start of a high-fat diet and decreases afterward. The recruitment of neutrophils to large arteries was found to depend on CCR1, CCR2, CCR5, and CXCR2, which contrasts to peripheral venous recruitment, which requires CCR2 and CXCR2 only. The involvement of CCR1 and CCR5 corresponded to the endothelial deposition of the platelet-derived chemokine CCL5 in arteries but not in veins.
CONCLUSIONS: Our data provide evidence that hypercholesterolemia-induced neutrophilia is multifactorial and that neutrophils infiltrate arteries primarily during early stages of atherosclerosis. Collectively, these data suggest an important role of neutrophils in the initiation of atherosclerosis.
Maik Drechsler; Remco T A Megens; Marc van Zandvoort; Christian Weber; Oliver Soehnlein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-18
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2010-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1837-45     Citation Subset:  AIM; IM    
Institute for Molecular Cardiovascular Research, Pauwelsstrasse 30, 52074 Aachen, Germany.
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MeSH Terms
Apolipoproteins E / deficiency,  genetics
Arteries / cytology,  metabolism
Atherosclerosis / etiology,  metabolism,  physiopathology*
Chemokines / metabolism
Disease Models, Animal
Hypercholesterolemia / complications,  metabolism,  physiopathology*
Mice, Inbred C57BL
Mice, Knockout
Neutrophils / cytology,  physiology*
Receptors, CCR1 / metabolism
Receptors, CCR5 / metabolism
Reg. No./Substance:
0/Apolipoproteins E; 0/Ccr1 protein, mouse; 0/Chemokines; 0/Receptors, CCR1; 0/Receptors, CCR5
Comment In:
Circulation. 2010 Nov 2;122(18):1786-8   [PMID:  20956213 ]

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