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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:601.)
© 2003 American Heart Association, Inc.

Vascular Biology

Low Density Lipoproteins Interact With Acidic Fibroblast Growth Factor and Modify Its Function

Natalya Ananyeva; Alexey Tjurmin; Evgueni Saenko; Christian Haudenschild

From the Departments of Experimental Pathology (A.T., C.H.) and Biochemistry (N.A., E.S.), Holland Laboratory, American Red Cross, Rockville, Md.

Correspondence to Natalya Ananyeva, PhD, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855. E-mail ananyeva{at}usa.redcross.org

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.

Key Words: acidic fibroblast growth factor • oxidized LDL • complex formation • proteoglycan • atherogenesis

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