Abstract
Basic fibroblast growth factor (bFGF) is a potent smooth muscle cell mitogen. Smooth muscle cell and macrophage-derived foam cells, resulting from cholesteryl ester accretion, are hallmark characteristics of atherosclerosis. We wanted to determine if bFGF synthesis is altered during cholesteryl ester accumulation in smooth muscle cells. Cholesteryl ester enrichment causes a 3-fold increase in bFGF in cellular lysates and a 3-fold increase in steady state mRNA levels for bFGF, as compared with control cells. Conditioned media from cholesteryl ester-enriched smooth muscle cells contains 6 times more mitogenic activity than conditioned media from control cells; this activity is neutralized by an antibody directed against bFGF but not by an antibody directed against platelet-derived growth factor. These results suggest that cholesteryl ester enrichment also enhances bFGF release. Since oxysterols have been implicated in the pathogenesis of atherosclerosis, we determined if oxysterols could affect bFGF production and release. 25-Hydroxycholesterol also increases the release of bFGF-like mitogens from smooth muscle cells, as well as increasing mRNA transcript levels for bFGF. Cholesteryl ester enrichment and 25-hydroxycholesterol did not promote bFGF release secondary to cell injury. In conclusion, these data define a basic mechanism for smooth muscle cell hyperplasia during atherogenesis involving the generation of bFGF by smooth muscle cell-derived foam cells.
Highlights
Basic fibroblast growth factor’ is a member of a growing family of heparin-binding growth factors and is a potent mitogen for mesenchymal cells, including smooth muscle cells.There aremultiple molecular weight speciesof Basic fibroblastgrowthfactor (bFGF), smooth muscle cells are a predominant cell type in the atherosclerotic plaque, and they accumulate lipid early during lesion progression [17]
We determined if cholesteryl ester enrichment altered bFGF gene expression and synthesisby smooth muscle cells
The i results suggest that theeffect of cholesteryl ester enrichment may be due to oxidized derivatives of cholesterol, since 25hydroxycholesterol, but not oxLDL, can alsoincrease bFGF
Summary
Increased Synthesis of bFGF by Smooth Muscle Cells in Response to Cholesteryl Ester Enrichment-Lysates from cholesteryl ester-enriched smooth muscle cellscontained 2 times the mitogenic activity, as compared with lysates from control cells (Fig. 1).This activity was not due to either cholesterol or cLDL, as neither of these agents increased [3H]thymidine incorporation in quiescent target cells Very little of the 3.3-kilobase mRNA wasexpressed in either control or cholesteryl ester-enriched smooth muscle cells.The increase in steady state mRNA levelsfor bFGF was maximal after 7days of treatment with cLDL (results notshown). Incontrast, lysates from cholesteryl ester-enriched (Fig. 3) when comparedwith the activity released from control smooth muscle cells contained immunoreactive bFGF levels cells, indicating that theresponse was not due to thenonspeof approximately 4-10 ng/mg of cell protein ( n = 4). To determine if the increase in mitogenic activity from cholesteryl ester-enriched smooth muscle cells wasdue to the presence of bFGF, conditioned media from control and cholesteryl ester-enriched smooth muscle cells weretreated with an antibody directed against bFGF as described in methods.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
