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Europe PMC Funders GroupAuthor Manuscript Endothelium. Author manuscript; out there in PMC 2006 March 13.Published in final edited type as: Endothelium. 2005 ; 12(5-6): 23341. doi:ten.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 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 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 lately extended towards the modulation of angiogenesis. Right here, to get more insight into the statins action, the authors have investigated the impact of atorvastatin on the expression of several 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 greater concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial development element (VEGF). Reduced 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 impacted. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may perhaps be of relevance towards the useful influence of statins in cardiovascular method.Keywords Atherosclerosis; PPARĪ“ Gene ID Cancer; Heme Oxygenase-1; Interleukin eight; Vascular Endothelial Development Factor Statins are potent inhibitors in the 3-hydroxy-3-methylglutaryl oenzyme A (HMG-CoA) reductase via blocking the substrate accessibility towards the enzyme and thereby successfully subverting cholesterol metabolism (for critiques see Kaushal et al. 2003; Undas et al. 2004; Liao and Laufs 2004). These effective drugs have, nonetheless, the 5-HT1 Receptor Inhibitor Source spectrum of activities significantly broader than may be explained only by reduce in cholesterol synthesis. They constituteAddress correspondence to J ef Dulak, PhD, DSc, Department 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 Research Fellow of Wellcome Trust.Dulak et al.Pagethe pleiotropic effects, which have been demonstrated to influence the production.