Cleaved XXXX accelerates the onset of endothelial progenitor cell senescence by induction of reactive @entity26 species.

@entity986 @entity26 @entity1441 @entity1435 @entity7199 @entity13474
OBJECTIVE: Cleaved @entity13474 (HKa), an activation product of the plasma @entity7199 -kinin system, inhibits endothelial cell functions. We questioned whether HKa affects the function of endothelial progenitor cells (EPCs) and accelerates their senescence. METHODS AND RESULTS: Treatment with HKa for 2 weeks markedly inhibited the formation of large colonies and proliferation of EPCs on collagen surfaces, whereas HKa did not affect collagen-mediated EPC adhesion and survival. Concomitantly, treated EPCs displayed flattened and giant cell morphological changes and formation of intracellular vacuoles. As determined by acidic b-galactosidase staining, HKa increased senescent EPCs by 2- and >3-fold after culture for 1 and 2 weeks, respectively. In addition, HKa suppressed the telomerase activity of EPCs. HKa concentration-dependently increased the generation of intracellular reactive @entity26 species (ROS) and markedly upregulated @entity1435 kinase phosphorylation and prosenescence molecule @entity986 ( @entity986 ) expression. @entity1441 , a @entity1435 inhibitor, attenuated the level of HKa-enhanced @entity986 ( @entity986 ) expression. Either quenching of ROS or inhibition of @entity1435 kinase prevented HKa-induced EPC senescence. CONCLUSIONS: HKa accelerates the onset of EPC senescence by activating the ROS- @entity1435 kinase- @entity986 ( @entity986 ) signaling cascade. This novel activity of HKa points out the likelihood of HKa serving as an endogenous inducer of EPC senescence.
