Inhibition of angiogenesis in vivo by plasminogen activator inhibitor-1

The process of angiogenesis is important in both normal and pathologic phys iology. However, the mechanisms whereby factors such as basic fibroblast gr owth factor promote the formation of new blood vessels are not known. In th e present study, we demonstrate that exogenously added plasminogen activato r inhibitor-1 (PAI-1) at therapeutic concentrations is a potent inhibitor o f basic fibroblast growth factor-induced angiogenesis in the chicken chorio allantoic membrane. By using specific PAI-1 mutants with either their vitro nectin binding or proteinase inhibitor activities ablated, we show that the inhibition of angiogenesis appears to occur via two distinct but apparentl y overlapping pathways. The first is dependent on PAI-1 inhibition of prote inase activity, most likely chicken plasmin, while the second is independen t of PAI-1's anti-proteinase activity and instead appears to act through PA I-1 binding to vitronectin. Together, these data suggest that PAI-1 may be an important factor regulating angiogenesis in vivo.