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.
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.
Kodama
Yasushi
Y
Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Nakakoma-gun, Yamanashi, Japan.
Kitta
Yoshinobu
Y
Nakamura
Takamitsu
T
Takano
Hajime
H
Umetani
Ken
K
Fujioka
Daisuke
D
Saito
Yukio
Y
Kawabata
Ken-ichi
K
Obata
Jyun-ei
JE
Mende
Akira
A
Kobayashi
Tsuyoshi
T
Kugiyama
Kiyotaka
K
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
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