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Europe PMC Funders GroupAuthor Manuscript Endothelium. Author manuscript; available in PMC 2006 March 13.Published in final edited kind as: Endothelium. 2005 ; 12(5-6): 23341. doi:ten.1080/10623320500476559.Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsAtorvastatin Affects A number of Angiogenic Mediators in Human Endothelial CellsJozef Dulak, Agnieszka Loboda, Agnieszka Jazwa, and Anna Zagorska Division of Medical Biotechnology, Faculty of Biotechnology, Jagiellonian University, Krak , Poland Jacob D ler, Hannes Alber, Wolfgang Dichtl, Franz Weidinger, and Matthias Frick Division of G-CSF R/CD114 Proteins Recombinant Proteins Cardiology, Innsbruck University, Austria Alicja Jozkowicz Department of Healthcare Biotechnology, Faculty of Biotechnology, Jagiellonian University, Krak , PolandAbstractThe pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl oenzyme A (HMGCoA) reductase, happen to be recently extended towards the modulation of angiogenesis. Right here, to have a lot more insight in to the statins action, the authors have investigated the impact of atorvastatin on the expression of various angiogenic and inflammatory genes in human umbilical endothelial cells (HUVECs). Atorvastatin was proangiogenic at the dose of ten nM, and antiangiogenic at the concentrations of 1 to ten M. Moreover, these greater concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial growth element (VEGF). Reduce doses of atorvastatin didn’t influence endothelial cell proliferation. Importantly, atorvastatin at the micromolar concentrations diminished the production of interleukin (IL)-8, a proinflammatory and proangiogenic chemokine, and inhibited the synthesis of urokinase plasminogen activator (uPA), a potent proinflammatory mediator. On the other hand, it decreased also the expression of plasminogen activator inhibitor-1 (PAI-1) and thrombospondin-1 (TSP-1), the inhibitors of angiogenesis. Atorvastatin stimulated the expression of angiopoietin (Ang)-2 and moderately enhanced the expression of endothelial nitric oxide synthase (eNOS), whereas heme oxygenase-1 (HO-1) was not drastically impacted. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may perhaps be of relevance to the useful influence of statins in cardiovascular program.Search phrases Atherosclerosis; Immunoglobulin-like Cell Adhesion Molecules Proteins MedChemExpress Cancer; Heme Oxygenase-1; Interleukin eight; Vascular Endothelial Growth Aspect Statins are potent inhibitors with the 3-hydroxy-3-methylglutaryl oenzyme A (HMG-CoA) reductase by means of blocking the substrate accessibility towards the enzyme and thereby properly subverting cholesterol metabolism (for testimonials see Kaushal et al. 2003; Undas et al. 2004; Liao and Laufs 2004). Those effective drugs have, even so, the spectrum of activities significantly broader than could possibly be explained only by reduce in cholesterol synthesis. They constituteAddress correspondence to J ef Dulak, PhD, DSc, Division of Medical Biotechnology, Faculty of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krak , Poland. E-mail: [email protected]. Supported by Pfizer, Poland, PBZ-KBN-107/P04/2004 and by the Polish-Austrian Collaborative Grant (17/2002). Dr Jozkowicz is an International Senior Analysis Fellow of Wellcome Trust.Dulak et al.Pagethe pleiotropic effects, which have already been demonstrated to influence the production.