title: Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease.
abstract: OBJECTIVE
  The aim of this study was to test a possible influence of atorvastatin on the production of vascular endothelial growth factor (VEGF) in patients with coronary artery disease (CAD) and in vitro.
  
  
  BACKGROUND
  Vascular endothelial growth factor is suggested to be involved in the growth of atherosclerotic plaque by inducing its neovascularization. Hepatic hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statins) are known to have atheroprotective effects beyond lipid lowering.
  
  
  METHODS
  Blood was collected from 14 male hypercholesterolemic patients with angiographically confirmed CAD at baseline and after two months of atorvastatin therapy (20 mg/d) and from eight male control patients. In an ex vivo assay, human coronary artery smooth muscle cells (HCASMC) were incubated with the patient plasma collected before and after atorvastatin therapy. To test the direct effect of atorvastatin on VEGF synthesis in vitro, HCASMC were treated with atorvastatin (1, 3 and 10 microM). The VEGF concentration was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Atorvastatin therapy reduced VEGF plasma levels in CAD patients (from 31.1 +/- 6.1 to 19.0 +/- 3.6 pg/ml; p < 0.05). The VEGF plasma concentration tended to be higher in CAD patients before treatment compared to control patients (31.1 +/- 6.1 vs. 23.4 +/- 3.6 pg/ml; p = NS). Plasma collected before therapy induced significantly more VEGF in HCASMC compared to the plasma collected after treatment and compared to control cells. In vitro, atorvastatin decreased both the basal and the interleukin-1beta-induced VEGF release in HCASMC.
  
  
  CONCLUSIONS
  These data suggest that atorvastatin may lower the plasma level of VEGF in CAD patients, which could represent a novel beneficial effect of this and perhaps other statins.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria.
authors.forename: Hannes Franz
authors.initials: HF
authors.lastname: Alber
authors.forename: Jozef
authors.initials: J
authors.lastname: Dulak
authors.forename: Matthias
authors.initials: M
authors.lastname: Frick
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dichtl
authors.forename: Severin Paul
authors.initials: SP
authors.lastname: Schwarzacher
authors.forename: Otmar
authors.initials: O
authors.lastname: Pachinger
authors.forename: Franz
authors.initials: F
authors.lastname: Weidinger
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D016228:Endothelial Growth Factors / Q000097:blood*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D016228:Endothelial Growth Factors; D006538:Heptanoic Acids; D008222:Lymphokines; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002784:Cholesterol; D000069059:Atorvastatin