Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the XXXX / @entity2215 pathway.

@entity2215 @entity2308 @entity63 @entity8562 @entity2307 @entity35 @entity731 @entity224 @entity2574
CONTEXT: Angelica sinensis (Oliv.) Diels (Apiaceae) polysaccharides ( @entity2574 ) may play a key role in anti- @entity63 activity. However, the anti- @entity731 activity and mechanism are unknown. OBJECTIVE: This study investigated the protective effects of @entity2574 against ox-LDL-induced senescence of EPCs and explored its underlying molecular mechanisms. MATERIALS AND METHODS: Mononuclear cells were isolated from bone marrow (BM) of SD @entity35 and differentiated to EPCs. EPCs were exposed to oxidized low-density lipoprotein (ox-LDL, 10     g/mL, 24   h) and incubated with or without high-dose (100     g/mL, 48   h) or low-dose (20     g/mL, 48   h) @entity2574 . Another group of EPCs was pre-treated with @entity2307 (100   nM, 45   min), a PI3K/ @entity2308 inhibitor. EPC senescence, telomerase activity, and @entity224 anion levels were assessed using SA-b-galactosidase staining, telomerase PCR-ELISA analysis, and DHE staining, respectively. The expression of related proteins, including @entity2308 , p- @entity2308 , @entity2215 , p- @entity2215 , and @entity8562 , were detected using western blot. RESULTS: EPCs (47.3%) were SA-b-gal positive after treatment by ox-LDL, additionally, ox-LDL significantly increased @entity224 anion levels (375% versus 100%), and inhibited telomerase activity (42% versus 100%). However, the pro-senescent effect of ox-LDL was attenuated about three-fold (16.7%), @entity224 anion levels were decreased more than two-fold (148%), and telomerase activity was recovered partly (88% versus 42%) in the EPCs when treated with @entity2574 (100     g/mL). The immunoblotting confirmed that @entity2574 attenuated inhibition of phosphorylation of @entity2308 and @entity2215 induced by ox-LDL and down-regulated increased the expression of gp91-phox. Moreover, some effects of @entity2574 were partially abrogated in the presence of @entity2307 . DISCUSSION: Ox-LDL induced senescence of EPCs via inhibition of telomerase activity, which was influenced by oxidative stress and the @entity2308 / @entity2215 pathway. The inhibition of EPC senescence by @entity2574 could be important for potential therapeutics. CONCLUSION: Treatment of EPCs with @entity2574 remarkably attenuates the harmful effects of ox-LDL via augmentation of @entity2308 / @entity2215 phosphorylation and inhibition of oxidative stress.
