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Europe PMC Funders GroupAuthor Manuscript Endothelium. Author manuscript; obtainable 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 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 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 been lately extended towards the modulation of angiogenesis. Here, to acquire much more insight in to the statins action, the authors have investigated the impact of atorvastatin on the expression of quite a few 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. In addition, these higher concentrations inhibited also the proliferation of 5-HT4 Receptor Inhibitor MedChemExpress 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 RSK3 custom synthesis potent proinflammatory mediator. Nevertheless, 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 impacted. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may well be of relevance to the beneficial influence of statins in cardiovascular program.Search phrases Atherosclerosis; Cancer; Heme Oxygenase-1; Interleukin 8; Vascular Endothelial Growth Issue Statins are potent inhibitors of your 3-hydroxy-3-methylglutaryl oenzyme A (HMG-CoA) reductase through blocking the substrate accessibility to the enzyme and thereby successfully subverting cholesterol metabolism (for reviews see Kaushal et al. 2003; Undas et al. 2004; Liao and Laufs 2004). Those efficient drugs have, however, the spectrum of activities much broader than might be explained only by reduce in cholesterol synthesis. They constituteAddress correspondence to J ef Dulak, PhD, DSc, Department 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 Research Fellow of Wellcome Trust.Dulak et al.Pagethe pleiotropic effects, which have been demonstrated to influence the production.