on April 3, 2003
Published online before print April 3, 2003, doi: 10.1161/01.ATV.0000069624.55424.61
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Submitted on January 24, 2003
Accepted on March 6, 2003
Fibroblast Growth Factor-2, But Not Vascular Endothelial Growth Factor, Upregulates Telomerase Activity in Human Endothelial Cells
David J. Kurz ;
From the Cell Biology Group (D.J.K., Y.H., E.T., H.-L.H., S.D., G.H.Z., J.D.E.), British Heart Foundation Laboratories, Department of Medicine, University College London, London, UK, and Department of Cardiovascular Research (D.J.K., T.F.L.), Institute of Physiology, University of Zurich, and Department of Cardiology, University Hospital, Zurich, Switzerland.
* To whom correspondence should be addressed. E-mail: j.erusalimsky{at}ucl.ac.uk.
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).
Methods and 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 hTER--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.
Key words: telomerase • fibroblast growth factor-2 • endothelial cell • Sp1 • senescence
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