Angiotensin-converting enzyme inhibition restores hepatocyte growth factorproduction in patients with congestive heart failure

Endothelium-dependent vasodilation is imp aired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectivel y against endothelial dysfunction. HGF production is downregulated by angio tensin II (Ang II) in vitro. We hypothesized that HGF production is impaire d as the result of increased Ang II in patients with congestive heart failu re, and that if so, the impaired production should be restored with angiote nsin-converting enzyme inhibitors (ACE-I). We studied 16 patients with cong estive heart failure caused by previous anterior myocardial infarction in w hom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximate to 4 weeks after the treatment with ACE-I, blood samples were c ollected to measure the levels of HGF, Ang II, and brain natriuretic peptid e as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was signif icantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I dec reased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response, In conclusion, impaired HGF production was restored after the tr eatment with ACE-I probably by the mechanism of Ang II suppression. This no vel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implicatio n.