Shear stress depends on the phosphatidylinositol 3-kinase/forkhead-like transcription factor signaling pathway to improve mesenteric arteriole dilation in aging rats
Shear stress depends on the phosphatidylinositol 3-kinase/forkhead-like transcription factor signaling pathway to improve mesenteric arteriole dilation in aging rats
Objective To determine the effect of high fluid shear stress on aging vessels and the underlying mechanism.Methods Male rats(6 and 24 months old)were selected to establish a model of high flow in mesenteric arterioles.The mesenteric arteries were isolated 3 weeks later.There were four groups with 10 rats in each group,as follows:young+normal flow(NF);young+high flow(HF);old+NF;and old+HF.Arterial elasticity was detected by vascular perfusion.The nitric oxide(NO)level in the arterial perfus-ate was measured using a biochemical method.Western blot was used to detect the levels of serine/threo-nine kinase(Akt)protein and the phosphorylation(p-Akt)form,forkhead-like transcription factor(FoxO1)protein and the phosphorylation(p-FoxO1)form,and the B lymphocystoma 2 gene(Bcl-2)and the associated X protein(Bax),and cysteine protease 3(Caspase-3).To verify the role of phosphatidylino-sitol 3-kinase(PI3K)in the function of high fluid shear stress on blood vessels,the PI3K inhibitor,wort-mannin(15 μg/kg),was administered to rats with established high fluid shear stress,and the mesenteric arteries were isolated 24 h later.NO and related protein expression were measured.Results Compared with the young+NF group,p-Akt,p-FoxO1,and Bcl-2Bax were decreased,while caspase-3 expression was increased in the old+NF group.Compared with the young+NF group,vascular elasticity increased with no significant difference in the young+HF group,the levels of p-Akt and p-FoxO1 protein were up-regulated,the expression of Bcl-2/Bax was increased,and the expression of caspase-3 was decreased.Compared with the old+NF group,the old+HF group exhibited significantly improved vascular elasticity,increased NO re-lease,increased expression of p-Akt,p-FoxO1,and Bcl-2/Bax,and decreased expression of caspase-3.Inhibition of PI3K with wortmannin significantly inhibited the expression of p-Akt and p-FoxO1 induced by HF.After inhibition of PI3K with wortmannin,the NO content in HF vascular perfusion fluid in the young and old groups was significantly lower than the group not treated with wortmannin;the difference was statis-tically significant(P<0.05).Conclusions High fluid shear stress stimulates NO release via the PI3K/Akt/FoxO1 signaling pathway,which subsequently suppressed the decrease in arterial elasticity that occurs with aging.In addition,HF reduced apoptosis to delay vascular aging.
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