Role of Heparin-induced HGF Release at the Acute Phase of STEMI

Simon Leboube^1,2*Alexandre Paccalet^1,2Camille BRUN²Florentin MOULIN²Bruno Pillot²Gabriel Bidaux²Laura MECHTOUFF^1,2Hélène THIBAULT^1,2Thomas BOCHATON^1,2Claire CROLA DA SILVA²

• ¹Hospices Civils de Lyon, Lyon, France
• ²Cardiovasculaire Metabolisme Diabetologie et Nutrition, Pierre-Bénite, France

Introduction: Reperfusion injury remains a major limitation in the management of ST-segment elevation myocardial infarction (STEMI). Despite numerous preclinical successes, cardioprotective strategies have largely failed in clinical translation. Heparin, routinely administered in STEMI, may exert protective effects beyond anticoagulation through rapid release of hepatocyte growth factor (HGF), a known cardioprotective agent. Methods: We analyzed 229 STEMI patients undergoing primary percutaneous coronary intervention (PCI) from the HIBISCUS-STEMI cohort. Serum HGF levels were measured by ELISA at five time points post-admission. In a subset of four patients, HGF levels were assessed before and 30 minutes after heparin injection. To test the functional effect of HGF, a murine ischemia-reperfusion model was used where recombinant HGF (0.3 mg/kg) or saline was administered intravenously five minutes before reperfusion. Infarct size was quantified by TTC staining. Results: A rapid and significant rise in HGF levels was observed at admission (median 8750 pg/mL), declining thereafter. In the subset analysis, heparin administration increased HGF levels from 356 ± 77 to 5026 ± 1957 pg/mL (p < 0.05). In mice, HGF administration significantly reduced infarct size compared to controls (48% vs. 58%, p = 0.0023), with no difference in area at risk. Discussion: This study demonstrates that heparin induces a rapid and substantial increase in circulating HGF in STEMI patients, potentially mediating cardioprotection during reperfusion. These findings suggest that co-medications like heparin may confound cardioprotective trials and should be considered in future translational strategies.