Premium
Effects of endothelin‐1 on endothelial progenitor cell function
Author(s) -
Diehl Kyle J,
Westby Christian M,
Weil Brian R,
MacEneaney Owen J,
Morgan Richard G,
Mestek Michael L,
Kushner Erich J,
Van Engelenburg Alexander M,
DeSouza Christopher A
Publication year - 2009
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.23.1_supplement.965.14
Subject(s) - progenitor cell , apoptosis , endothelin 1 , endothelial progenitor cell , vasoprotective , clonogenic assay , endothelium , endothelin receptor , staurosporine , endothelial stem cell , angiogenesis , tunel assay , microbiology and biotechnology , chemistry , biology , receptor , immunology , pharmacology , endocrinology , medicine , stem cell , cancer research , signal transduction , in vitro , nitric oxide , biochemistry , protein kinase c
Circulating endothelial progenitor cells (EPCs) play an important role in maintaining and repairing the vascular endothelium and restoring functional activity. Endothelin (ET)‐1, a potent vasoconstrictor peptide, is released by the endothelium and contributes to endothelial damage and atherogenesis. The effects of ET‐1 on EPC function are unknown. We tested the hypothesis that ET‐1 impairs EPC function. Peripheral blood samples were collected from 10 healthy adult humans. Cells with phenotypic EPC characteristics were isolated and EPC clonogenic (colony forming unit assay) and migratory (Boyden chamber) capacity as well as apoptotic susceptibility (TUNEL assay) were determined in the absence and presence and ET‐1 (100 pM). The number of EPC colony‐forming units (42±12 vs. 39±11) and migratory capacity (910±146 vs. 936±148) was not significantly different between the ET‐1 treated and untreated cells. In response to staurosporine (1 mM), EPCs treated with ET‐1 demonstrated a 20% increase (P<0.05) in cellular apoptosis. The proapoptotic effect of ET‐1 was abolished with ET receptor blockade as well as with apocynin, an NADPH inhibitor. These results indicate that ET‐1 does not affect EPC colony formation or migratory capacity but does increase EPC susceptibility to apoptosis through a NADPH‐dependent mechanism. Increased EPC apoptosis may contribute to the proatherogenic effects of ET‐1.