Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
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).
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 559-561 |
Seitenumfang | 3 |
Fachzeitschrift | FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
Jahrgang | 20 |
Ausgabenummer | 3 |
Publikationsstatus | Veröffentlicht - März 2006 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 33645838815 |
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Schlagworte
Schlagwörter
- Aged, Aged, 80 and over, Aminocaproic Acid/pharmacology, Angiostatins/pharmacology, Apolipoproteins A/metabolism, Aspirin/pharmacology, Atherosclerosis/physiopathology, Cell Movement, Cells, Cultured/cytology, Chemotaxis, Leukocyte/physiology, Coronary Artery Disease/metabolism, Coronary Vessels/chemistry, Endothelial Cells/cytology, Endothelium, Vascular/cytology, Female, Gene Expression Regulation, Homocysteine/pharmacology, Humans, Intercellular Adhesion Molecule-1/metabolism, Lipoprotein(a)/pharmacology, Lymphocyte Function-Associated Antigen-1/metabolism, Macrophage-1 Antigen/chemistry, Male, Middle Aged, Monocytes/cytology, NF-kappa B/metabolism, Plasminogen/pharmacology, Protein Binding, Protein Structure, Tertiary, Transfection