Effect of intravenous heparin on serum levels of endostatin, VEGF and HGF: author's reply.

We read with interest the article by Seko and colleagues [1], who document that serum levels of endostatin and VEGF (vascular endothelial growth factor) are increased markedly in patients with acute myocardial infarction, but subsequently decrease significantly by early reperfusion. We would like to point out important limitations in their findings not addressed in the study. This relates entirely to the administration of intravenous heparin during the reperfusion process. Firstly, we disagree that the significant decrease seen in serum VEGF levels 3–6 h after reperfusion relates to a down-regulation of VEGF production, but, in fact, is entirely due to intravenous heparin administration, which is known to modulate the interaction of VEGF with its receptor [2]. Kawamoto et al. [3] found that the serum concentration of VEGF in patients with acute myocardial infarction was reduced by up to 93 % 1 h after administration of intravenous heparin. Secondly, endostatin is also a heparin-binding protein [4], and the measurement of serum levels after heparin administration is also likely to show a significant decrease. This may explain why Seko and colleagues [1] found a similar pattern of change in serum levels of VEGF and endostatin before and after reperfusion. Thirdly, serum HGF (hepatocyte growth factor) levels are known to increase dramatically within 30 min after intravenous administration of heparin [5], which also explains the significant increase in HGF levels after