OXIDIZED LDL MEDIATES THE RELEASE OF FIBROBLAST GROWTH-FACTOR-I

Citation
Nm. Ananyeva et al., OXIDIZED LDL MEDIATES THE RELEASE OF FIBROBLAST GROWTH-FACTOR-I, Arteriosclerosis, thrombosis, and vascular biology, 17(3), 1997, pp. 445-453
Citations number
64
Categorie Soggetti
Peripheal Vascular Diseas
ISSN journal
10795642
Volume
17
Issue
3
Year of publication
1997
Pages
445 - 453
Database
ISI
SICI code
1079-5642(1997)17:3<445:OLMTRO>2.0.ZU;2-F
Abstract
Fibroblast growth factor-1 (FGF-1) and lipoproteins play an important role in atherogenesis. In the present study, we explored a possible me chanism by which abnormal lipid metabolism could be linked to the prol iferative aspects of the disease. We tested oxidized LDL (oxLDL) as a possible pathophysiological mediator of the release of FGF-1, using FG F-1-transfected mouse NIH 3T3 cells and FGF-1-transfected rabbit smoot h muscle cells, and compared it with the release caused by elevated te mperature. Immunoblot analysis showed that oxLDL induced the release o f FGF-1 in a concentration-dependent manner from 10 to 100 mu g/mL. Th e effect correlated with the extent of oxidative modification of LDL a nd was maximal within 4 hours of exposure of cells to oxLDL. In contra st to the temperature stress-induced FGF-1 secretion pathway, FGF-1 re leased in response to oxLDL (1) appeared in the conditioned medium as a monomer: (2) appeared independently of the presence of either actino mycin D or cycloheximide, and (3) was neither enhanced nor inhibited b y brefeldin A. We did not detect cell loss, significant morphological changes, changes in growth characteristics, or other indications of le thal toxicity in oxLDL-treated cells. Although the level of lactate de hydrogenase activity was elevated after oxLDL exposure, the calculatio ns showed that >90% of the FGF-1 was released by viable cells. We prop ose that oxLDL-induced FGF-1 release is mediated by sublethal and appa rently transient changes in cell membrane permeability. In the environ ment of an atherosclerotic lesion, oxLDL-induced FGF-1 release may be among the mediators of endothelial and smooth muscle cell proliferatio n.