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CLINICAL RESEARCH

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

Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

Manuscript received January 6, 2006; revised manuscript received February 22, 2006, accepted March 6, 2006.

^_* Reprint requests and correspondence: Dr. Kiyotaka Kugiyama, Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Nakakoma-gun, Yamanashi, 409-3898 Japan (Email: kugiyama{at}yamanashi.ac.jp).

OBJECTIVES: 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.

Abbreviations and Acronyms   ACS = acute coronary syndrome   AMI = acute myocardial infarction   CAD = coronary artery disease   Flt-1 = Fms-like tyrosine kinase 1   LDL = low-density lipoprotein   LVEDVI = left ventricular end-diastolic volume index   LVEF = left ventricular ejection fraction   LVESVI = left ventricular end-systolic volume index   MI = myocardial infarction   PlGF = placental growth factor   VEGF = vascular endothelial growth factor

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