Exercise-Induced Hepatocyte Growth Factor Production in Patients after Acute Myocardial Infarction - Its Relationship to Exercise Capacity and Brain Natriuretic Peptide Levels

Background: The hepatocyte growth factor (HGF) is a multifunctional cytokine with cardioprotective properties and potent myogenic activity for vascular endothelium. In patients after acute myocardial infarction, exercise training has the beneficial effects on cardiovascular adaptations. We hypothesized that exercise induces HGF production in those patients. If this hypothesis is correct, HGF production may be associated with clinical parameters of cardiovascular function. Methods and Results: In 20 patients after acute myocardial infarction, HGF levels in the pulmonary artery (HGFPA) and aorta (HGFAo) were determined at rest and during supine submaximal exercise, with cardiac output (CO) measured by catheterization. Exercise-induced HGF production was calculated by using the following equation: [(HGFPA-HGFAo)× CO during exercise] - [(HGFPA-HGFAo)×CO at rest]. On a separate day, peak oxygen uptake (V̇O2) was determined during a symptom-limited upright cardiopulmonary exercise test. Exercise increased HGF production (from 1.6±3.0 to 9.0±6.3 μg/ml, p < 0.001). Exercise-induced HGF production was inversely related to peak V̇O2 (r=-0.664, p < 0.01) and positively related to levels of brain natriuretic peptide (BNP), a biochemical marker for post-infarction ventricular remodeling (r=0.686, p < 0.01). Conclusions: Exercise significantly increases HGF production. This phenomenon may play an important role in post-infarction patients, particularly with reduced exercise tolerance and elevated BNP levels.