| Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. | |
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MedLine Citation:
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PMID: 16403785 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NFkappaB, as well as the NFkappaB-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a). |
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Authors:
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Sotirios N Sotiriou; Valeria V Orlova; Nadia Al-Fakhri; Eveliina Ihanus; Matina Economopoulou; Berend Isermann; Khalil Bdeir; Peter P Nawroth; Klaus T Preissner; Carl G Gahmberg; Marlys L Koschinsky; Triantafyllos Chavakis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-01-10 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 20 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-03-01 Completed Date: 2006-04-21 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 559-61 Citation Subset: IM |
Affiliation:
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Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland 20892, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Aminocaproic Acid
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pharmacology Aged Aged, 80 and over Angiostatins / pharmacology Apolipoproteins A / metabolism Aspirin / pharmacology Atherosclerosis / physiopathology* Cell Movement Cells, Cultured / cytology, drug effects Chemotaxis, Leukocyte / physiology* Coronary Artery Disease / metabolism, pathology, physiopathology Coronary Vessels / chemistry, pathology Endothelial Cells / cytology, metabolism Endothelium, Vascular / cytology Female Gene Expression Regulation Homocysteine / pharmacology Humans Intercellular Adhesion Molecule-1 / metabolism Lipoprotein(a) / pharmacology, physiology* Lymphocyte Function-Associated Antigen-1 / metabolism Macrophage-1 Antigen / chemistry, physiology* Male Middle Aged Monocytes / cytology, metabolism* NF-kappa B / metabolism Plasminogen / pharmacology Protein Binding Protein Structure, Tertiary Transfection |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins A; 0/Lipoprotein(a); 0/Lymphocyte Function-Associated Antigen-1; 0/Macrophage-1 Antigen; 0/NF-kappa B; 126547-89-5/Intercellular Adhesion Molecule-1; 454-28-4/Homocysteine; 50-78-2/Aspirin; 60-32-2/6-Aminocaproic Acid; 86090-08-6/Angiostatins; 9001-91-6/Plasminogen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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