Role Of AMPK/mTOR Signaling Pathway In The Formation Of Abdominal Aortic Aneurysm And Its Molecular Mechanism

Objective:To study the expression of adenosine monophosphate-activated protein kinase(AMPK)and mammalian target of rapamycin(m TOR)signaling in AAA and VSMC,To investigate the role of AMPK / m TOR in the formation of AAA and its molecular mechanism,to provide a theoretical basis for the prevention and treatment of AAA.Methods: In this study,32 cases of human AAA tissue were selected as the experimental group,and 20 normal abdominal aortic tissues were used as negative control group(NC).The expression of AMPK,p-AMPK,p-m TOR,p70S6 K and4EBP1 protein was detected by western blot.Histochemical staining was used to detect the expression of p-AMPK,p-m TOR,p70S6 K and 4EBP1.Human VSMC(HVSMC)was cultured and treated with a gradient of AMPK agonist AICAR and inhibitor Compound C.CCK8 assay was used to determine the optimal concentration of HVSMC proliferation,the expression of p-AMPK,p-m TOR,p70S6 K,4EBP1protein was detected by western blot.Results : There was no significant difference in AMPK expression between AAA group and NC group(P>0.05).The expression of p-AMPK in NC group was significantly higher than that in AAA group(P<0.05),the expression of p-m TOR,p70S6 K and 4EBP1 in NC group was significantly lower than that in AAA group(P<0.05).Immunohistochemical staining indicated that p-AMPK,p-m TOR,p70S6 K and 4EBP1 were mainly expressed in VSMCs.In vitro cultured HVSMC,activation of AMPK expression can lead to decreased expression of p-m TOR,p70S6 K,4EBP1;while inhibition of AMPK expression,p-m TOR,p70S6 K,4EBP1 expression was increased.Conclusions:The expression of p-AMPK was decreased in AAA and the expression of p-m TOR,p70S6 K,and 4EBP1 was increased in AAA.The activation and inhibition of AMPK can regulate the expression of p-m TOR,p70S6 K and 4EBP1 in cultured HVSMC.This suggests that the AMPK/m TOR signaling pathway may be a new target for AAA prevention and control.