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Europe PMC Funders GroupAuthor Manuscript Endothelium. Author manuscript; available in PMC 2006 March 13.Published in final edited form as: Endothelium. 2005 ; 12(5-6): 23341. doi:10.1080/10623320500476559.Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsAtorvastatin Affects Many Angiogenic Mediators in Human Endothelial CellsJozef Dulak, Agnieszka Loboda, Agnieszka Jazwa, and Anna Zagorska Adenosine A2B receptor (A2BR) Antagonist Formulation Division of Health-related Biotechnology, Faculty of Biotechnology, Jagiellonian University, Krak , Poland Jacob D ler, Hannes Alber, Wolfgang Nav1.8 custom synthesis Dichtl, Franz Weidinger, and Matthias Frick Division of Cardiology, Innsbruck University, Austria Alicja Jozkowicz Department of Medical Biotechnology, Faculty of Biotechnology, Jagiellonian University, Krak , PolandAbstractThe pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl oenzyme A (HMGCoA) reductase, have been lately extended to the modulation of angiogenesis. Here, to obtain far more insight into the statins action, the authors have investigated the effect 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 in the concentrations of 1 to 10 M. Additionally, these higher concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial development factor (VEGF). Reduced doses of atorvastatin did not 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. However, 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 considerably affected. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may perhaps be of relevance to the valuable influence of statins in cardiovascular program.Keywords and phrases Atherosclerosis; 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 through blocking the substrate accessibility for the enzyme and thereby successfully subverting cholesterol metabolism (for reviews see Kaushal et al. 2003; Undas et al. 2004; Liao and Laufs 2004). These effective drugs have, nevertheless, the spectrum of activities substantially broader than may be explained only by lower in cholesterol synthesis. They constituteAddress correspondence to J ef Dulak, PhD, DSc, Division of Healthcare 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 definitely an International Senior Analysis Fellow of Wellcome Trust.Dulak et al.Pagethe pleiotropic effects, which happen to be demonstrated to influence the production.