Immediate Increase in Circulating Hepatocyte Growth Factor/Scatter Factor by Heparin

Circulating levels of hepatocyte growth factor (HGF)/scatter factor have been recently found to be increased in the early phase of myocardial infarction, and it has been hypothesized that HGF plays a role in angiogenesis and collateral vessel growth. Heparin has also been shown to enhance angiogenesis and to improve collateral blood flow. This study was designed to study the effect of heparin on the release of HGF. In an experimental study, heparin was given to rats intravenously and plasma was collected for measurements of HGF by enzyme-linked immunosorbent assay. A dose-dependent increase in circulating HGF was measured with peak levels occurring 10 min after injection of 300 units/kg of heparin (15.4±2.0 ng/ml afterv0.17±0.14 ng/ml before injection,P<0.0001). In a subsequent clinical study, 12 patients received 3000 units of heparin during cardiac catheterization. Circulating HGF increased steeply within 3 min of the injection. Comparable changes in plasma concentrations were measured in samples obtained from femoral vein (8.7±3.5 afterv0.33±0.07 before injectionP<0.05) or artery (10.5±3.2 ng/mlv0.27±0.05P<0.01), pulmonary artery (9.1±2.0 ng/mlv0.36±0.06 ng/ml,P=0.07 ) or right atrium (8.5±1.6 ng/mlv0.42±0.11,P<0.01).This study suggests that heparin-induced effects such as the promotion of angiogenesis may be at least partly due to the release of HGF.