Document Detail


Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin.
MedLine Citation:
PMID:  16403785     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-10
Journal Detail:
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:
Created Date:  2006-03-01     Completed Date:  2006-04-21     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  559-61     Citation Subset:  IM    
Affiliation:
Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
6-Aminocaproic Acid / 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:
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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