Fibroblast growth factor-2, but not vascular endothelial growth factor, upregulates telomerase activity in human endothelial cells.
OBJECTIVE
Telomerase plays a major role in the control of replicative capacity, a critical property for successful angiogenesis and maintenance of endothelial integrity. In this study, we examined the relationship between telomerase activity and endothelial cell proliferation as well as the regulation of this enzyme by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-A (VEGF).


RESULTS
Telomerase was repressed in endothelial cells freshly derived from intact endothelium, whereas activity was present during logarithmic growth in culture. In cultured human umbilical vein endothelial cells (HUVECs), mRNA levels of hTERT-the catalytic subunit of telomerase-and enzyme activity decreased reversibly on induction of quiescence. Treatment of quiescent HUVECs with FGF-2 restored telomerase activity in a time- and dose-dependent manner, whereas VEGF had no such effect, although both factors induced comparable mitogenic responses. FGF-2, but not VEGF, upregulated the mRNA levels for hTERT and for the hTERT gene transactivation factor Sp1. Serial passage in the presence of individual growth factors accelerated the accumulation of senescent cells in VEGF-treated cultures compared with cultures treated with FGF-2.


CONCLUSIONS
FGF-2, but not VEGF, restores telomerase activity and maintains the replicative capacity of endothelial cells.
Kurz
David J
DJ
Cell Biology Group, British Heart Foundation Laboratories, Department of Medicine, University College London, London, UK.
Hong
Ying
Y
Trivier
Elizabeth
E
Huang
Hsiu-Lin
HL
Decary
Stephanie
S
Zang
Guo Hong
GH
Lüscher
Thomas F
TF
Erusalimsky
Jorge D
JD
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D004268:DNA-Binding Proteins; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D016259:Genes, myc; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016329:Sp1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D016329:Sp1 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019098:Telomerase