title: Atorvastatin increases plasma soluble Fms-like tyrosine kinase-1 and decreases vascular endothelial growth factor and placental growth factor in association with improvement of ventricular function in acute myocardial infarction.
abstract: OBJECTIVE
  This study examined whether atorvastatin increases plasma levels of soluble Fms-like tyrosine kinase 1 (sFlt-1) and reciprocally decreases vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with acute myocardial infarction (AMI).
  
  
  BACKGROUND
  Statins exert cardioprotective actions partly through anti-inflammatory actions. By capturing VEGF and PlGF in plasma, sFlt-1 acts as a natural inhibitor of VEGF and PlGF, which have proinflammatory properties.
  
  
  METHODS
  Left ventriculography and enzyme-linked immunosorbent assay of plasma levels of sFlt-1, VEGF, and PlGF were repeated after AMI in 50 consecutive patients with a first AMI. Patients were randomized to treatment with atorvastatin (10 mg/day; n=25) or placebo (n=25) within 3 days after AMI, and therapy was continued for 6 months.
  
  
  RESULTS
  The sFlt-1 levels were low in the acute phase, followed by an increase at 2 weeks after AMI, whereas free VEGF and PlGF levels were high in the acute phase, followed by a decrease at 2 weeks. Atorvastatin increased sFlt-1 levels and reciprocally decreased VEGF and PlGF levels at 6 months compared with placebo. The increase in sFlt-1 levels and the decrease in VEGF and PlGF levels were correlated with improvement of left ventricular ejection fraction during the follow-up period.
  
  
  CONCLUSIONS
  There was a reciprocal relationship between changes in sFlt-1 levels and changes in VEGF and PlGF levels after AMI; and atorvastatin increased sFlt-1 levels while decreasing VEGF and PlGF levels. These changes were associated with late improvement of post-MI ventricular function, and may represent an additional benefit of statin therapy.
authors.affiliation: Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Nakakoma-gun, Yamanashi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kodama
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kitta
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Takano
authors.forename: Ken
authors.initials: K
authors.lastname: Umetani
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Jyun-ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Akira
authors.initials: A
authors.lastname: Mende
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D000069059:Atorvastatin; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006133:Growth Substances / Q000097:blood*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood*; D011758:Pyrroles / Q000627:therapeutic use*; D013318:Stroke Volume; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D016277:Ventricular Function, Left
chemical_list: D006133:Growth Substances; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D000069059:Atorvastatin; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1