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Cleaved high molecular weight kininogen accelerates endothelial progenitor cell senescence via induction of reactive oxygen species
Author(s) -
Dai Jihong,
Wu Yi
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.750.10
Subject(s) - high molecular weight kininogen , kininogen , senescence , progenitor cell , microbiology and biotechnology , endothelial progenitor cell , chemistry , biology , kallikrein , biochemistry , stem cell , enzyme
High‐molecular‐weight kininogen (HK) is a component of the plasma kallikrein‐kinin system (KKS) and plays a central role in the activation of this system. Upon cleavage by plasma kellikrein, HK is converted into cleaved form of HK (HKa), which gains a function of antiadhesion and antiangiogenesis. In this study, we further investigated whether HKa regulates the functions of endothelial progenitor cells (EPCs). Our observations demonstrate that HKa at 50 mM markedly inhibited colony formation as well as proliferation of EPCs as assessed by BrdU incorporation assay. This effect did not result from its antiadhesive activity and induction of apoptosis, because HKa failed to inhibit EPC adhesion to collagen surfaces and did not increase the percentage of apoptotic cells. In the absence of HKa, EPCs became slightly senescent as determined by acidic ¦Â‐galactosidase staining. HKa, however, significantly accelerated the onset of EPC senescence. Since reduced form of glutathione, an ROS scavenger, prevented the increase in acidic ¦Â‐galactosidase‐positive cells, HKa acceleration of EPC senescence is through ROS production. Taken together, the present study demonstrates a novel role for HKa in inhibition of EPC function, and suggests the likelihood for HKa serving as endogenous inducer of EPC dysfunction by accelerating the onset of EPC senescence.