Abstract
Accumulating evidence suggests an important role of Phosphatidylinositol 3-kinease (PI3K) pathway in inflammatory cells infiltration. Given the essential role of inflammatory cells infiltration during the formation and progression of abdominal aortic aneurysm (AAA), to investigate the possibility of preventing AAA formation and progression via targeting PI3K is anticipated. Here, experimental AAAs was created in rats by transient intraluminal porcine pancreatic elastase (PPE) infusion into the infrarenal aorta firstly. AAAs rats were administrated with vehicle or Wortmannin during the period of day 0 to day 28 after PPE infusion. The aortic diameter of rats treated with Wortmannin was significantly smaller than those treated with vehicle. Meanwhile, Elastin destruction score and SMC destruction score were significantly decreased in rats treated with Wortmannin. Furthermore, histological analysis revealed infiltration of inflammatory cells were significantly reduced in rats treated with Wortmannin. Finally, the mRNA expression of PI3K and protein expression of pAKT in human abdominal aneurismal aorta tissues was elevated as compare to normal aorta. Our study revealed that PI3K inhibitor suppresses experimental AAAs formation and progression, through mechanisms likely related to impairing inflammation cells infiltration and median elastin degradation. These findings indicated that PI3K inhibitor may hold substantial translation value for AAA diseases.
Highlights
Abdominal aortic aneurysm (AAA) is a common degenerative disease of the abdominal aorta that leads to its dilatation and to rupture
Experimental abdominal aortic aneurysm (AAA) model created by transient intra-aortic infusion of porcine pancreatic elastase (PPE) was extensively employed for the aneurysm research because this model correctly simulates the pathological features of human
Vernier caliper was employed to measure the diameter of aorta directly underwent laparotomy at day 0 and day 28 after PPE infusion
Summary
PI3K and pAKT are up-regulated in experimental aneurismal aorta. To investigate the potential role of PI3K in progression of AAA, an experimental abdominal aortic aneurysm was built up in rats firstly as described in previous[15]. 2D,E, both elastin destruction score and SMC destruction score were significantly decreased in rats treated with Wortmannin (P < 0.05) Together, these results indicated that PI3K inhibitor treatment inhibits experimental AAA formation and progression. Whereas the expression of VEGF was significantly decreased in aneurismal aorta tissue after Wortmannin treatment (P < 0.05) Together, these results indicated that PI3K inhibitor treatment inhibit AAA progression may be through inhibition of pAKT/VEGF signal pathway. The expression of mRNA levels of PI3K showed a general tendency of positive correlation with medical history such as thrombus and smoking, whereas negative correlation with medical history such as diabetes (P > 0.05) These results suggested a potential translational value of PI3K in inhibition of human AAA. These results supported a potential translational value of PI3K in inhibition of human AAA
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