氧化低密度脂蛋白對內皮細胞BFGF基因表達之轉錄及後轉錄調制(2/2)
Other Title
Oxidized Low-Density Lipoproteins Inhibit Endothelial Cell
Proliferation by Suppressing Basic Fibroblast Growth
Factor Expression
Proliferation by Suppressing Basic Fibroblast Growth
Factor Expression
Date Issued
2000
Date
2000
Author(s)
李源德
DOI
892314B002029
Abstract
Background—Hyperlipidemia inhibits proliferation of endothelial cells (ECs) in culture and angiogenesis in vivo and in
arterial explants. Elucidation of the mechanisms may suggest novel therapies against atherosclerosis.
Methods and Results—Basic fibroblast growth factor (bFGF) expression and mitogenic effects were assessed in bovine
aortic ECs incubated with oxidized LDL (ox-LDL). Compared with native LDL and lipoprotein-free controls, ox-LDL
reduced bFGF mRNA levels in a time- and concentration-dependent manner, 100 mg/mL producing a maximum
reduction of 40% to 50% within 24 to 48 hours. There were commensurate reductions in intracellular and extracellular
bFGF concentrations, DNA and total RNA syntheses, and cell replication. FGF receptor 1 and b-actin mRNA levels
were unchanged. Ox-LDL accelerated bFGF mRNA degradation in actinomycin D–treated cells. However, inhibition
of bFGF expression by ox-LDL was attenuated by cyclohexamide, indicating a requirement for continuous new protein
synthesis for posttranscriptional destabilization. Reduced syntheses of DNA and total RNA were completely restored by
bFGF but not by vascular endothelial growth factor. Inhibition of total RNA synthesis achieved by exposing cells to a
bFGF-neutralizing antibody was similar in magnitude to that induced by ox-LDL.
Conclusions—Cytotoxic effects of ox-LDL on ECs are attributable in part to suppression of bFGF expression.
Subjects
lipoproteins
growth substances
endothelium
genes
angiogenesis
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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