Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the Akt/hTERT pathway. (2nd December 2015)

• Record Type: Journal Article
• Authors: Lai, Peng; Liu, Yixin
• Is Part Of: Pharmaceutical biology. Volume 53:Number 12(2015:Dec.)
• Page Start: 1842
• Page End: 1849
• Publication Date: 2015-12-02
• Subjects: EPCs -- gp91-phox -- ox-LDL -- superoxide anion -- telomerase; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.3109/13880209.2015.1027779
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context : Angelica sinensis (Oliv.) Diels (Apiaceae) polysaccharides (ASP) may play a key role in anti-ischemic activity. However, the anti-atherosclerotic activity and mechanism are unknown. Objective : This study investigated the protective effects of ASP 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 rats and differentiated to EPCs. EPCs were exposed to oxidized low-density lipoprotein (ox-LDL, 10 µg/mL, 24 h) and incubated with or without high-dose (100 µg/mL, 48 h) or low-dose (20 µg/mL, 48 h) ASP. Another group of EPCs was pre-treated with Wortmannin (100 nM, 45 min), a PI3K/Akt inhibitor. EPC senescence, telomerase activity, and superoxide anion levels were assessed using SA-β-galactosidase staining, telomerase PCR-ELISA analysis, and DHE staining, respectively. The expression of related proteins, including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western blot. Results : EPCs (47.3%) were SA-β-gal positive after treatment by ox-LDL, additionally, ox-LDL significantly increased superoxide 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%), superoxide anion levels were decreased more than two-fold (148%), and telomerase activity was recovered partly (88% versus 42%) in the EPCs when treated with ASP (100 µg/mL). The immunoblotting confirmed that ASP attenuated inhibition of phosphorylation of Akt and hTERT induced by ox-LDL and down-regulated increased the expression of gp91-phox. Moreover, some effects of ASP were partially abrogated in the presence of Wortmannin. Discussion : Ox-LDL induced senescence of EPCs via inhibition of telomerase activity, which was influenced by oxidative stress and the Akt/hTERT pathway. The inhibition of EPC senescence by ASP could be important for potential therapeutics. Conclusion : Treatment of EPCs with ASP remarkably attenuates the harmful effects of ox-LDL via augmentation of Akt/hTERT phosphorylation and inhibition of oxidative stress.