title: Atorvastatin affects several angiogenic mediators in human endothelial cells.
abstract: The pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been recently extended to the modulation of angiogenesis. Here, to get more insight into the statins action, the authors have investigated the effect 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 micro M. Moreover, these higher concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial growth factor (VEGF). Lower 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 significantly affected. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may be of relevance to the beneficial influence of statins in cardiovascular system.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland. jdulak@mol.uj.edu.pl
authors.forename: Józef
authors.initials: J
authors.lastname: Dulak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Loboda
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jazwa
authors.forename: Anna
authors.initials: A
authors.lastname: Zagorska
authors.forename: Jacob
authors.initials: J
authors.lastname: Dörler
authors.forename: Hannes
authors.initials: H
authors.lastname: Alber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dichtl
authors.forename: Franz
authors.initials: F
authors.lastname: Weidinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Frick
authors.forename: Alicja
authors.initials: A
authors.lastname: Jozkowicz
mesh_terms: D000069059:Atorvastatin; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D011758:Pyrroles; D000069059:Atorvastatin