Document Detail


Low density lipoproteins interact with acidic fibroblast growth factor and modify its function.
MedLine Citation:
PMID:  12692004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Oxidized LDL (oxLDL) was shown to trigger the release of acidic fibroblast growth factor (FGF-1). Because these components are likely to be present simultaneously in the atherosclerotic milieu, we investigated whether oxLDL interacts with FGF-1 and whether this interaction affects FGF-1 functioning. METHODS AND RESULTS: Using molecular sieve and electrophoretic mobility shift assays, we found that FGF-1 forms a complex with oxLDL in vitro, in contrast to its low affinity for nonatherogenic, native LDL. The FGF-1/oxLDL complex had a dramatically decreased ability to bind heparin and was nonmitogenic on cultured smooth muscle cells. In human atherosclerotic lesions, the highest FGF-1 immunoreactivity was found in macrophages. With respect to oxLDL accumulation, 2 patterns were distinguished: (1) moderate, intracellular in matrix-rich regions containing viable cells and (2) massive, both cell-associated and extracellular oxLDL deposits in foam cell-rich regions with necrotic areas. The proliferating cell nuclear antigen readings for proliferating cells reflected that the mitogenic activity of FGF-1 was confined to the regions where oxLDL was strictly intracellular and was inhibited in the regions with extracellular oxLDL deposition. CONCLUSIONS: oxLDL, besides being a bulky component of the atherosclerotic lesion, possibly manifests its pathogenicity by complexing FGF-1 and inhibiting its growth-promoting function during atherogenesis.
Authors:
Natalya Ananyeva; Alexey Tjurmin; Evgueni Saenko; Christian Haudenschild
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-03-06
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  23     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-14     Completed Date:  2004-01-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  601-7     Citation Subset:  IM    
Affiliation:
Department of Experimental Pathology, American Red Cross, 15601 Crabbs Branch Way, Rockville, Md 20855, USA. ananyeva@usa.redcross.org
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MeSH Terms
Descriptor/Qualifier:
Coronary Artery Disease / metabolism,  pathology
Fibroblast Growth Factor 1 / metabolism,  pharmacology*,  secretion
Foam Cells / metabolism
Heparin / metabolism
Humans
Lipoproteins, LDL / pharmacology*
Macromolecular Substances
Macrophages / metabolism
Peptide Fragments / pharmacology
Protein Binding / drug effects
Recombinant Proteins / pharmacology
Grant Support
ID/Acronym/Agency:
HL 54246/HL/NHLBI NIH HHS; HL66101/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipoproteins, LDL; 0/Macromolecular Substances; 0/Peptide Fragments; 0/Recombinant Proteins; 0/fibroblast growth factor-1 (21-154), human; 0/oxidized low density lipoprotein; 104781-85-3/Fibroblast Growth Factor 1; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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