Negative Regulation of Local Hepatocyte Growth Factor Expression by Angiotensin II and Transforming Growth Factor-β in Blood Vessels

Abstract

—Because hepatocyte growth factor (HGF) is a member of the endothelium-specific growth factors, we hypothesized that HGF may play a role in cardiovascular disease. Therefore we first examined the role of local HGF production in endothelial cell (EC) growth. Addition of anti-HGF antibody to EC resulted in a significant decrease in EC number. Moreover, coculture of vascular smooth muscle cells (VSMC) with EC resulted in an increase in EC number that was completely inhibited by anti-HGF antibody, suggesting that HGF secreted from EC and VSMC regulates EC growth in an autocrine-paracrine manner. Interestingly, transforming growth factor (TGF)-β significantly decreased HGF secretion from EC, whereas interleukin 6 stimulated immunoreactive HGF secretion. In human VSMC, TGF-β and angiotensin II suppressed local HGF production in a dose-dependent manner. Interestingly, anti–TGF-β antibody resulted in significant but not complete inhibition of the decrease in local HGF production. To further study the regu...