# Role of heparin-induced HGF release in the acute phase of STEMI

## TL;DR

This study shows that heparin increases heart-protecting HGF in STEMI patients, which could explain why some heart treatments fail in clinical trials.

## Contribution

The novel finding is that heparin rapidly boosts HGF levels in STEMI patients, potentially confounding cardioprotective trials.

## Key findings

- Heparin administration significantly increased HGF levels in STEMI patients within 30 minutes.
- HGF administration in mice reduced infarct size during ischemia-reperfusion injury.
- HGF levels in patients peaked at admission and declined afterward.

## Abstract

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 for STEMI, may exert protective effects beyond anticoagulation through a rapid release of hepatocyte growth factor (HGF), a known cardioprotective agent.

In this study, we analyzed 229 STEMI patients undergoing primary percutaneous coronary intervention from the HIBISCUS-STEMI cohort. Serum HGF levels were measured by using ELISA at five time points post admission. In a subset of four patients, HGF levels were assessed before and 30 min 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 2,3,5-triphenyltetrazolium chloride staining.

A rapid and significant rise in HGF levels was observed at admission (median 8,750 pg/mL), declining thereafter. In the subset analysis, heparin administration increased HGF levels from 356 ± 77 to 5,026 ± 1,957 pg/mL (p < 0.05). In mice, HGF administration significantly reduced the infarct size compared with controls (48% vs. 58%, p = 0.0023), with no difference in the area at risk.

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 comedications like heparin may confound cardioprotective trials and should be considered in future translational strategies.