1. ¹Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria
2. ²Department of Dermatology, Medical University of Vienna, Vienna, Austria
3. ³GSF-National Research Center for Environment and Health, Institute of Molecular Virology, Neuherberg, Germany
4. ⁴Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen, Erlangen, Germany
5. ⁵Centre de Recherches et Investigation Epidermiques et Sensorielles (CE.R.I.E.S.), Neuilly, France

Correspondence: Dr E Tschachler, MD, Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail: erwin.tschachler@meduniwien.ac.at

Received 22 July 2005; Revised 30 June 2006; Accepted 30 June 2006; Published online 7 August 2006.

Abstract

Although the antiangiogenic activity of type I interferons (IFN) is well known, the mechanism by which it occurs is unclear. In the present study, we have investigated effects of short-term and long-term IFN- exposure on different types of endothelial cells (EC). Short-term IFN- treatment resulted in a distinct reduction of apoptosis of serum and growth factor starved HUVEC and HDMEC. This was accompanied by a strong upregulation of the IFN inducible guanylate binding protein-1 (GBP-1) whereas no consistent regulation of several known antiapoptotic proteins was evident. Stable transfection of HUVEC with an expression vector for GBP-1 mimicked the protective effect of IFN-, suggesting that GBP-1 may contribute to the inhibition of apoptosis. When IFN-, together with serum and EC growth factors, was present continuously a decrease of population doublings by more than 40% was observed in both HDMEC and HCAEC. In addition, the cells displayed a senescent phenotype significantly earlier than control cells and showed an increased adherence for monocytes. Our findings suggest that the antiangiogenic effect of IFN- is mediated by inducing EC senescence rather than EC apoptosis. Furthermore IFN- released in chronic inflammatory conditions might contribute via its prosenescent activity to the pathogenesis of atherosclerosis.