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Europe PMC Funders GroupAuthor 5-HT3 Receptor Antagonist Molecular Weight Manuscript Endothelium. Author manuscript; obtainable in PMC 2006 March 13.Published in final edited kind as: Endothelium. 2005 ; 12(5-6): 23341. doi:10.1080/10623320500476559.Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsAtorvastatin Impacts Numerous 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 Cardiology, Innsbruck University, Austria Alicja Jozkowicz Division of Health-related Biotechnology, Faculty of Biotechnology, Jagiellonian University, Krak , PolandAbstractThe pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl oenzyme A (HMGCoA) reductase, have already been recently extended for the modulation of NPY Y1 receptor review angiogenesis. Here, to have much 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 10 nM, and antiangiogenic at the concentrations of 1 to 10 M. Additionally, these larger concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial growth aspect (VEGF). Lower doses of atorvastatin did not influence endothelial cell proliferation. Importantly, atorvastatin in 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. Even so, 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 for the effective influence of statins in cardiovascular system.Search phrases Atherosclerosis; Cancer; Heme Oxygenase-1; Interleukin eight; Vascular Endothelial Growth Aspect Statins are potent inhibitors of your 3-hydroxy-3-methylglutaryl oenzyme A (HMG-CoA) reductase by means of blocking the substrate accessibility to the enzyme and thereby correctly subverting cholesterol metabolism (for reviews see Kaushal et al. 2003; Undas et al. 2004; Liao and Laufs 2004). These efficient drugs have, having said that, the spectrum of activities significantly broader than could possibly be explained only by decrease 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 Investigation Fellow of Wellcome Trust.Dulak et al.Pagethe pleiotropic effects, which have been demonstrated to influence the production.