Salidroside exerts angiogenic and cytoprotective effects on human bone marrow‐derived endothelial progenitor cells via Akt/mTOR/p70S6K and MAPK signalling pathways

Background and Purpose With the increase of age, increased susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells ( EPC s). The aim of this study was to investigate whether salidroside ( SAL ) can induce angiogenic differentiation and inhibit oxidative stress‐induced apoptosis in bone marrow‐derived EPC s ( BM ‐ EPC s), and if so, through what mechanism. Experimental Approach BM‐EPC s were isolated and treated with different concentrations of SAL for up to 4 days. Cell proliferation, migration and tube formation ability were detected by DNA content quantification, transwell assay and M atrigel‐based angiogenesis assay. Gene and protein expression were assessed by qRT‐PCR and W estern blot respectively. Key Results Treatment with SAL promoted cellular proliferation and angiogenic differentiation of BM‐EPC s, and increased VEGF and NO secretion, which in turn mediated the enhanced angiogenic differentiation of BM‐EPC s. Furthermore, SAL significantly attenuated hydrogen peroxide ( H 2 O 2 )‐induced cell apoptosis, reduced the intracellular level of reactive oxygen species and restored the mitochondrial membrane potential of BM‐EPC s. Moreover, SAL stimulated the phosphorylation of A kt, mammalian target of rapamycin and p70 S 6 kinase, as well as ERK 1/2, which is associated with cell migration and capillary tube formation. Additionally, SAL reversed the phosphorylation of JNK and p38 MAPK induced by H 2 O 2 and suppressed the changes in the Bax / Bcl ‐ xL ratio observed after stimulation with H 2 O 2 . Conclusions and Implications These findings identify novel mechanisms that regulate EPC function and suggest that SAL has therapeutic potential as a new agent to enhance vasculogenesis as well as protect against oxidative endothelial injury.