Hepatocyte growth factor plasma levels after myocardial infarction are notaffected by recombinant tissue-type plasminogen-activator therapy

Hepatocyte growth factor (HGF), a cytokine involved in tissue regeneration, angiogenesis and lateral vessel growth, is secreted as a biological-inacti ve, single-chain precursor named pro-HGF. In case, of tissue injury pro-HGF is proteolytically cleaved at the extracellular locus by serine proteases. Results obtained from in vitro experiments showed that urokinase-type plas minogen activator (uPA) and tissue-type plasminogen activator (tPA) can cle ave single-chain HGF. In this study we measured serum HGF levels in patient s with acute myocardial infarction (MCI). Two groups of patients were compa red. One group (n = 7) was treated with a conventional therapy and the othe r group (n = 7) was subjected to a thrombolytic therapy with recombinant ti ssue-type plasminogen activator (rtPA). Serum samples were collected at tim e of admission and subsequently 12-16 hours, 20-30 hours and 50-60 hours af ter onset of chest pain. At admission and before administration of rtPA, se rum HGF levels peaked at 16.8 +/- 2.2 ng/ml in the lysed group and at 20.7 +/- 6.5 ng/ml in the non-lysed group. Levels then continuously declined, re aching lowest values 50-60 hours after onset of chest pain (3.2 +/- 1.3 ng/ ml in the group treated with rtPA versus 4.4 +/- 0.9 ng/ml in the non-lysed group). No statistical significant difference could be detected between th e two groups at any time. We suggest that serine proteases other than tPA a re involved in HGF activation in vivo.