Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors.
It appears that there are two classes of human circulating endothelial cell (EC) progenitors, CD34+ and CD34-CD14+ cells. Attention has focused on CD34+ cells, yet CD34-CD14+ monocytic cells are far more abundant and may represent the most common class of circulating EC progenitor. Little is known about molecular or physiological factors that regulate putative CD34-CD14+ EC progenitor function, although factors secreted by other blood and cardiovascular cells to which they are exposed probably affect their behavior. Hypoxia and stretch are two important physiological stimuli known to trigger growth factors in cardiovascular cells and accordingly may modulate EC progenitors. To investigate the impact of these environmental parameters on EC progenitors, EC production in CD34-CD14+ cultures was evaluated. Our data indicate that neither stretch nor hypoxia alters EC production by EC progenitors directly but do so indirectly through their effects on cardiovascular cells. Conditioned media (CM) from coronary artery smooth muscle cells inhibit EC production in culture, and this inhibition is stronger if the coronary smooth muscle cells have been subjected to cyclic stretch. In contrast, cardiomyocyte CM increases EC cell number, an effect that is potentiated if the myocytes have been subjected to hypoxia. Significantly, EC progenitor responses to CM are altered by the presence of CD34-CD14- peripheral blood mononuclear cells (PBMCs). Moreover, CD34-CD14- PBMCs attenuate EC progenitor responsiveness to the angiogenic factors basic fibroblast growth factor (FGF-2), vascular endothelial cell growth factor-A165, and erythropoietin while inducing EC progenitor death in the presence of transforming growth factor-beta1 in vitro
Wang
Chunlin
C
Department of Exercise Science, University of Iowa, Iowa City, Iowa 52242, USA.
Jiao
Chunhua
C
Hanlon
Heather D
HD
Zheng
Wei
W
Tomanek
Robert J
RJ
Schatteman
Gina C
GC
D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002319:Cardiovascular System / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D003470:Culture Media; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004921:Erythropoietin