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Europe PMC CD48 Proteins Purity & Documentation Funders GroupAuthor Manuscript Endothelium. Author manuscript; accessible in PMC 2006 March 13.Published in final edited form 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 Department of Healthcare 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 , NTB-A Proteins MedChemExpress PolandAbstractThe pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl oenzyme A (HMGCoA) reductase, have been lately extended towards the modulation of angiogenesis. Right here, to get extra insight into the statins action, the authors have investigated the impact of atorvastatin on the expression of many angiogenic and inflammatory genes in human umbilical endothelial cells (HUVECs). Atorvastatin was proangiogenic in the dose of ten nM, and antiangiogenic in the concentrations of 1 to 10 M. Furthermore, these greater concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial growth aspect (VEGF). Decrease 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. 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 might be of relevance towards the helpful influence of statins in cardiovascular system.Search phrases Atherosclerosis; Cancer; Heme Oxygenase-1; Interleukin 8; Vascular Endothelial Development Element Statins are potent inhibitors from the 3-hydroxy-3-methylglutaryl oenzyme A (HMG-CoA) reductase by way of 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 efficient drugs have, however, the spectrum of activities significantly broader than may very well be explained only by lower 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 Study Fellow of Wellcome Trust.Dulak et al.Pagethe pleiotropic effects, which have already been demonstrated to influence the production.
