Ox-LDL modifies the behavior of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
Chu, Ling × Hao, Hong Luo, Min Huang, Yu Chen, Zhenyu Lu, Tiewei Zhao, Xue Verfaillie, Catherine Zweier, Jay L Liu, Zhenguo #
Carol Davila University Press
Journal of Cellular and Molecular Medicine vol:15 issue:2 pages:423-432
Abstract This study was to investigate the effect of oxidized low density lipoprotein (ox-LDL) on the behavior of bone marrow stem cells and their endothelial differentiation as well as the underlying mechanisms. Adult rat bone marrow multipotent progenitor cells (MAPCs) were incubated with ox-LDL for up to 2 weeks. Ox-LDL treatment resulted in a time- and dose-dependent reduction of MAPC population in culture through a combination of decreased cell proliferation and increased apoptosis. The expression of stem cell marker Oct-4 was significantly suppressed in MAPCs by ox-LDL in a dose- and time-dependant manner. Endothelial differentiation of MAPCs was substantially inhibited by ox-LDL with markedly decreased expression of endothelial markers vWF, Flk-1, and CD31, as well as impaired in vitro vascular structure formation. Ox-LDL-induced apoptosis and inhibition of Oct-4 expression, cell proliferation, and endothelial differentiation of MAPCs were associated with significant inhibition of Akt phosphorylation. Akt overexpression in MAPCs transfected with a constitutively active Akt completely reversed the effects of ox-LDL on MAPCs including enhanced apoptosis, decreased cell proliferation, suppressed Oct-4 expression and endothelial differentiation as well as in vitro vascular structure formation. In conclusion, ox-LDL promotes apoptosis and inhibits Oct-4 expression and self-renewal of MAPCs, and impairs their endothelial differentiation via suppression of Akt signaling.