Objective: To describe a novel approach, 3D printing guiding stent graft fenestration, for fenestration during endovascular aneurysm repair for juxtarenal abdominal aortic aneurysm. Methods: A 69-year-old male with juxtarenal abdominal aortic aneurysm underwent endovascular aneurysm repair with “off the label” fenestrated stent graft. To precisely locate the fenestration position, we reconstructed a 3D digital abdominal aortic aneurysm model and created a skin template covering this abdominal aortic aneurysm model. Then the skin template was physically printed and the position of the visceral vessel was hollowed out, thereby helping in locating the fenestration on stent graft. Results and conclusions: With the help of this 3D printed skin template, we fenestrated the stent graft accurately and rebuilt the bilateral renal artery successfully. This is the first clinical case that used 3D printing guiding stent graft fenestration, which is a novel approach for precise fenestration on stent graft on the table during endovascular aneurysm repair.

Background: The protective effects of polyamines on cardiovascular disease have been demonstrated in many studies. However, the roles of spermidine, a natural polyamine, in abdominal aortic aneurysm ( AAA ) disease have not been studied. In this study, we investigated the influence and potential mechanisms of spermidine treatment on experimental AAA disease. Methods and Results: Experimental AAA s were induced in 8‐ to 10‐week‐old male C57 BL /6J mice by transient intra‐aortic infusion of porcine pancreatic elastase. Spermidine was administered via drinking water at a concentration of 3 mmol/L. Spermidine treatment prevented experimental AAA formation with preservation of medial elastin and smooth muscle cells. In immunostaining, macrophages, T cells, neutrophils, and neovessels were significantly reduced in aorta of spermidine‐treated, as compared with vehicle‐treated elastase‐infused mice. Additionally, flow cytometric analysis showed that spermidine treatment reduced aortic leukocyte infiltration and circulating inflammatory cells. Furthermore, we demonstrated that spermidine treatment promoted autophagy‐related proteins in experimental AAA s using Western blot analysis, immunostaining, and transmission electron microscopic examination. Autophagic function was evaluated for human abdominal aneurysmal and nonaneurysmal adjacent aortae from AAA patients using Western blot analysis and immunohistochemistry. Dysregulated autophagic function, as evidenced by increased SQSTM 1/p62 protein and phosphorylated mTOR , was found in aneurysmal, as compared with nonaneurysmal, aortic segments. Conclusions: Our results suggest that spermidine supplementation limits experimental AAA formation associated with preserved aortic structural integrity, attenuated aortic inflammatory infiltration, reduced circulating inflammatory monocytes, and increased autophagy‐related proteins. These findings suggest that spermidine may be a promising treatment for AAA disease.

Accumulating evidence in recent years has demonstrated the important role of gut microbiota in maintaining cardiovascular function. However, their functions in abdominal aortic aneurysm (AAA) are largely unexplored. In this study, we established a porcine pancreatic elastase-infused experimental AAA mouse model and explored gut microbiota modulation using 16S rDNA sequencing. Here, we found that a significant alteration to gut microbiota composition and function occurred in AAA. The functional change in the gut microbiome revealed dysregulated biosynthesis metabolism and transport of spermidine in AAA. Furthermore, exogenous spermidine was administrated via drinking water and attenuated the progression of experimental AAA disease, which supports our recent study that spermidine alleviates systemic inflammation and AAA. These effects were associated with remitted gut microbiota dysbiosis and metabolism in AAA progression as demonstrated by 16S rDNA gene analysis. In addition, several bacterial florae, such as Bacteroides, Parabacteroides and Prevotella, were identified to be associated with the progression of AAA. Our results uncovered altered gut microbial profiles in AAA and highlighted the potential therapeutic use of spermidine in the treatment of gut microbiota dysbiosis and AAA.

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.

Abdominal aortic aneurysm (AAA) is one of the most life-threatening cardiovascular diseases; however, effective drug treatments are still lacking. The formation of neutrophil extracellular traps (NETs) has been shown to be a crucial trigger of AAA, and identifying upstream regulatory targets is thus key to discovering therapeutic agents for AAA. We revealed that phosphoinositide-3-kinase γ (PI3Kγ) acted as an upstream regulatory molecule and that PI3Kγ inhibition reduced NET formation and aortic wall inflammation, thereby markedly ameliorating AAA. However, the mechanism of NET formation regulated by PI3Kγ remains unclear. In this study, we showed that PI3Kγ deficiency inactivated the noncanonical pyroptosis pathway, which suppressed downstream NET formation. In addition, PI3Kγ regulation of noncanonical pyroptosis was dependent on cyclic AMP/protein kinase A signaling. These results clarify the molecular mechanism and crosstalk between PI3Kγ and NETosis in the development of AAA, potentially facilitating the discovery of therapeutic options for AAA.