Low density lipoproteins interact with acidic fibroblast growth factor and modify its function.
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.


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.
Ananyeva
Natalya
N
Department of Experimental Pathology, American Red Cross, 15601 Crabbs Branch Way, Rockville, Md 20855, USA. ananyeva@usa.redcross.org
Tjurmin
Alexey
A
Saenko
Evgueni
E
Haudenschild
Christian
C
D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism / Q000494:pharmacology*; D005487:Foam Cells / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D046911:Macromolecular Substances; D008264:Macrophages / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
D008077:Lipoproteins, LDL; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011994:Recombinant Proteins; C480524:fibroblast growth factor-1 (21-154), human; C099252:oxidized low density lipoprotein; D016220:Fibroblast Growth Factor 1; D006493:Heparin