Evidence against the involvement of nitric oxide in the modulation of telomerase activity or replicative capacity of human endothelial cells.

Telomerase, a reverse transcriptase involved in the maintenance of telomere function and cellular replicative capacity, is thought to be regulated by nitric oxide (NO). Here, we have used pharmacological tools and RNA interference to re-assess the role of NO in the regulation of telomerase and senescence of human umbilical vein endothelial cells. Acute or chronic treatment of these cells with the NO donors diethylenetriamine/NO (DETA-NO) or S-nitroso-N-acetylpenicillamine (SNAP) at concentrations which generated NO in the 1-300 nM range did not modulate telomerase activity.

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).

Methods And Results: Telomerase was repressed in endothelial cells freshly derived from intact endothelium, whereas activity was present during logarithmic growth in culture.