Ox‐LDL Impairs Bone Marrow Stem Cell Differentiation into Endothelial Cells Possibly through Inhibition of Akt Phosphorylation

Abstract

In this study, experiments were designed to investigate the effects of oxidized low density lipoprotein (ox‐LDL) on bone marrow stem cell differentiation into endothelial cells and underlying mechanisms. Adult rat bone marrow multipotent progenitor cells (MAPCs) were used as the source of stem cells, and induced to differentiate into endothelial cells with or without ox‐LDL in the presence of VEGF. The differentiation process was closely monitored with cell morphology and expressions of endothelial markers including vWF, Flk‐1, and CD31 with RT‐PCR and Western blot analysis. As expected, the differentiating stem cells started to express vWF, Flk‐1, and CD31 from day 5 of differentiation, and reached their maximum at day 14. Ox‐LDL (at 9, 18, and 36 ug/ml) significantly inhibited the differentiation of MAPCs into endothelial cells in a dose‐dependent manner (p < 0.05) as reflected by markedly decreased mRNA levels and contents of vWF, Flk‐1, and CD31. Interestedly, the decreased expressions of endothelial markers were associated with significantly reduced Akt phosphorylation during the early phase of differentiation in these cells. These results indicate that ox‐LDL inhibits the differentiation of bone marrow stem cells into endothelial cells possibly through preventing Akt phosphorylation. The data from this study provides a novel mechanism for the development of ox‐LDL‐related cardiovascular diseases.