Specific blockade of basic fibroblast growth factor gene expression in endothelial cells by antisense oligonucleotide.
The migration and proliferation of endothelial cells play a pivotal role in various vascular diseases. To elucidate the role of endogenous basic fibroblast growth factor (bFGF) produced within endothelial cells on cell growth, we introduced the antisense oligonucleotide complementary to bFGF mRNA into cultured bovine aortic endothelial cells by cationic liposome to block the production of autocrine bFGF. The treatment of the endothelial cells with the specific antisense oligomer efficiently inhibited the synthesis of bFGF with the concomitant suppression of endothelial proliferation, indicating the significant role of bFGF as an endothelial growth promotor. The neutralizing antibody against bFGF had no inhibition on basal DNA synthesis of the endothelial cells, in contrast to marked suppressive action of bFGF antisense oligomer. The results provide the new analytic and therapeutic implications in the use of the antisense methodology for the study of vascular biology.
Itoh
H
H
Division of Cardiovascular Medicine, Stanford University Medical Center, CA 94305-5246.
Mukoyama
M
M
Pratt
R E
RE
Dzau
V J
VJ
D016475:3T3 Cells; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D014158:Transcription, Genetic
D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; D010714:Phosphatidylethanolamines; D005346:Fibroblast Growth Factors; C020888:1,2-dielaidoylphosphatidylethanolamine