Outcomes of standard EVAR for juxtarenal abdominal aortic aneurysm in patients unsuitable for fenestrated EVAR and open repair.

OBJECTIVE: To evaluate the long-term outcomes of standard endovascular aneurysm repair (S-EVAR) of juxtarenal abdominal aortic aneurysms (JAAAs). METHODS: Data of patients with JAAAs who were unsuitable for fenestrated endovascular aneurysm repair (F-EVAR) and open repair (OR) and underwent treatment from January 2015 to December 2021 were retrospectively reviewed. Computed tomography angiography and ultrasonography of the aorta were performed before discharge, at 6 and 12 months postoperatively, and annually thereafter. The main outcome measures were mortality, type Ia endoleaks, and reintervention. RESULTS: A total of 62 patients (mean age, 72.1 ± 7.3 years) underwent S-EVAR. The mean aneurysm length and diameter and the proximal neck length and diameter were 110.4 ± 30.9 mm, 57.2 ± 15.9 mm, 8.09 ± 0.97 mm, and 26.05 ± 0.49 mm, respectively. The mean suprarenal and infrarenal aortic angles were 162.9 ± 26° and 144.1 ± 31°, respectively. The mean follow-up duration was 40.6 ± 23.4 months and the 5-year survival rate was 62.2%. Six (9.8%) patients experienced type Ia endoleaks, of whom three underwent endovascular repair at 12, 18, and 24 months, one underwent conversion to OR for AAA rupture at 7 days and died, two had minor endoleaks and were kept under observation, and one declined reintervention at 36 months. The 5-year freedom from reintervention rate was 84.4%. The aneurysm diameter shrank in 50 cases (81%), remained stable in 5 cases (8%), and increased in 7 cases (11.3%). A suprarenal aortic angle <114° was associated with type Ia endoleak (p = .005). CONCLUSIONS: In patients unsuitable for F-EVAR and OR and with a suprarenal aortic angle >114°, the use of S-EVAR for JAAAs can be considered safe and effective. In this study, early and long-term postoperative outcomes demonstrated that S-EVAR achieved satisfactory results in the prevention of aneurysm rupture and associated mortality.

Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis.

Pterostilbene (PTE), a natural stilbene found in blueberries and several varieties of grapes, has several pharmacological activities, including anti-inflammatory and antioxidative activities. However, its role in abdominal aortic aneurysm (AAA), which is a severe inflammatory vascular disease, remains incompletely understood. In this study, we investigated the protective effects of natural stilbene PTE on AAA formation and the underlying mechanism. Two AAA mouse models (Ang II-induced model and PPE-induced model) were used to examine the effect of PTE on AAA formation. We showed that PTE administration attenuated AAA formation in mice. Furthermore, we found that PTE significantly inhibited inflammatory responses in mouse aortas, as PTE suppressed macrophage pyroptosis and prevented macrophage infiltration in aortas, resulting in reduced expression of pro-inflammatory cytokines in aortas. We also observed similar results in LPS + ATP-treated Raw 264.7 cells (a macrophage cell line) and primary peritoneal macrophages in vitro. We showed that pretreatment with PTE restrained inflammatory responses in macrophages by inhibiting macrophage pyroptosis. Mechanistically, miR-146a-5p and TRAF6 interventions in vivo and in vitro were used to investigate the role of the miR-146a-5p/TRAF6 axis in the beneficial effect of PTE on macrophage pyroptosis and AAA. We found that PTE inhibited macrophage pyroptosis by miR-146a-5p-mediated suppression of downstream TRAF6 expression. Moreover, miR-146a-5p knockout or TRAF6 overexpression abrogated the protective effect of PTE on macrophage pyroptosis and AAA formation. These findings suggest that miR-146a-5p/TRAF6 axis activation by PTE protects against macrophage pyroptosis and AAA formation. PTE might be a promising agent for preventing inflammatory vascular diseases, including AAA.

Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.

Background: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct. Methods and Results: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO. Conclusion: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.

D-Dimer Is a Diagnostic Biomarker of Abdominal Aortic Aneurysm in Patients With Peripheral Artery Disease.

Background: Etiology and risk factors of peripheral artery disease (PAD) include age, smoking, and hypertension, etc. , which are shared by an abdominal aortic aneurysm (AAA). Concomitance with AAA in patients with PAD is not rare but is easily overlooked in the clinical situation, though management strategies are altered totally. This study aims to investigate diagnostic biomarkers for the prediction of AAA in patients with PAD. Methods: A total of 684 patients diagnosed with AAA and/or PAD were enrolled and analyzed retrospectively. Each patient with PAD and AAA was gender and age-matched. Demographic data, medical history, and serum laboratory test profiles were obtained. Statistical analysis was performed to determine diagnostic biomarkers of AAA in patients with PAD. Results: Firstly, 320 patients with PAD-only and 320 patients with AAA-only were compared. Levels of bilirubin and D-Dimer were decreased, while the incidence of diabetes mellitus, levels of fibrinogen, and platelet count were increased significantly in patients with PAD-only compared with those in patients with AAA-only (P < 0.001). Next, 364 patients with PAD (44 patients with AAA) and 364 patients with AAA (44 patients with PAD) were compared. Multivariate logistic regression analysis confirmed the differential distribution of bilirubin, D-dimer, fibrinogen, and platelet count between patients with AAA and patients with PAD (P < 0.05). Receiver operator curves (ROC) showed that the area under the curve (AUC) of total bilirubin, direct bilirubin, D-dimer, fibrinogen, and platelet count was 0.6113, 0.5849, 0.7034, 0.6473, and 0.6785, respectively. Finally, to further validate the predictive efficacy of mentioned markers, a multivariable logistics regression analysis was performed between the PAD only group and the PAD with AAA group. The results suggested increased levels of D-dimer in the PAD with AAA group compared to the PAD only group (OR: 2.630, 95% CI:1.639-4.221; P < 0.001). In particular, the Youden index suggested that the cut-off value of D-dimer for predicting AAA in patients with PAD was 0.675 mg/L with a sensitivity of 76.9% and a specificity of 84.9% (AUC = 0.8673; 95% CI, 0.8106-0.9240, P < 0.001). In all 364 patients with PAD, 41.46% patients were diagnosed AAA when D-dimer is >0.675 mg/L, while only 3.55% patients were diagnosed AAA when D-dimer ≤ 0.675 mg/L. Conclusions: PAD and AAA exert different clinical and serum profiles; D-dimer (>0.675 mg/L) is a reliable biomarker for the prediction of AAA in patients with PAD.

Integrative analysis prioritizes the relevant genes and risk factors for chronic venous disease.

OBJECTIVE: Chronic venous disease (CVD) refers to a range of symptoms resulting from long-term morphological and functional abnormalities of the venous system. However, the mechanism of CVD development remains largely unknown. Here, we aim to provide more information on CVD pathogenesis, prevention strategies, and therapy development through the integrative analysis of large-scale genetic data. METHODS: Genetic data were obtained from publicly accessible databases. We used different approaches, including Functional Mapping and Annotation, DEPICT, Sherlock, SMR/HEIDIS, DEPICT, and NetWAS to identify possible causal genes for CVD. Candidate genes were prioritized to further literature-based review. The differential expression of prioritized genes was validated by microarray from the Gene Expression Omnibus, a public genomics data repository and real-time quantitative polymerase chain reaction of varicose vein specimens. The causal relationships between risk factors and CVD were assessed using the two-sample Mendelian randomization approach. RESULTS: We identified 46 lead single-nucleotide polymorphisms and 26 plausible causal genes for CVD. Microarray data indicated differential expression of possible causal genes in CVD when compared with controls. The expression levels of WDR92, RSPO3, LIMA, ABCB10, DNAJC7, C1S, and CXCL1 were significantly downregulated (P < .05). PHLDA1 and SERPINE1 were significantly upregulated (P < .05). Dysregulated expression of WDR92, RSPO3, and CASZ1 was also found in varicose vein specimens by quantitative polymerase chain reaction. Two-sample Mendelian randomization suggested causative effects of body mass index (odds ratio [OR], 1.008; 95% confidence interval [CI], 1.005-1.010), standing height (OR, 1.009; 95% CI, 1.007-1.011), college degree (OR, 0.983; 95% CI, 0.991-0.976), insulin (OR, 0.858; 95% CI, 0.794-0.928), and metformin (OR, 0.944; 95% CI, 0.904-0.985) on CVD. CONCLUSIONS: Our study integrates genetic and gene expression data to make an effective risk gene prediction and etiological inferences for CVD. Prioritized candidate genes provide more insights into CVD pathogenesis, and the causative effects of risk factors on CVD that deserve further investigation.

"Ring on Anastomosis" for Avoidance of Acute Proximal Anastomotic Leak after Open Surgical Repair of Abdominal Aortic Aneurysm.

BACKGROUND: Acute proximal anastomotic leak is among severe complications after open surgical repair (OSR) of abdominal aortic aneurysm. We have proposed an approach of "ring on anastomosis" (ROA) as a technical improvement of conventional OSR to reinforce proximal anastomotic section. METHODS: One hundred and nineteen abdominal aortic aneurysm patients admitted to Xiangya Hospital, Central South University were enrolled. Patients were randomly divided into conventional group (n = 54) and ROA group (n = 65). The ring is prepared by cutting out a 2-cm circle from the graft. Operative time, intraoperative blood loss, perioperative mortality, and retroperitoneal hematoma were recorded. Poisson distribution analysis was used between two groups. All methods were carried out in accordance with Declaration of Helsinki. RESULTS: No obvious difference in operative time or intraoperative blood loss was identified [(205.5 ± 6.535) versus (195.6 ± 6.034) minutes, P > 0.05; (756 ± 98.22) versus (673.1 ± 98.93) ml, P > 0.05, respectively]. Two patients in conventional group (2/54, 3.7%) died while no dead case was reported in ROA group (P = 0.047). Three cases in conventional group experienced retroperitoneal hematoma while none was witnessed in ROA group (P = 0.027). An average of 18 months of follow-up was obtained in all patients, and no proximal anastomotic stenosis was reported. CONCLUSIONS: As a technical improvement of conventional OSR, ROA reinforces aorta graft anastomotic section and diminishes anastomotic leak as well as perioperative death without extra cost of time and money.

The role of autophagy in abdominal aortic aneurysm: protective but dysfunctional.

Autophagy, an evolutionarily conserved mechanism that promotes cell survival by recycling nutrients and degrading long-lived proteins and dysfunctional organelles, is an important defense mechanism, and its attenuation has been well documented in senescence and aging-related diseases. Abdominal aortic aneurysm (AAA), a well-known aging-related disease, has been defined as a chronic degenerative process in the abdominal aortic wall; however, the complete mechanism is unknown, and a clinical treatment is lacking. Accumulating evidence has recently revealed that numerous drugs that can induce autophagy are effective in the treatment of AAA. The purpose of this systematic review was to focus on the cross-talk between autophagy and high-risk factors and the potential pathogenesis of AAA to understand not only the host defense and pathogenesis but also potential treatments.

Inhibition of Phosphatidylinositol 3-Kinase γ by IPI-549 Attenuates Abdominal Aortic Aneurysm Formation in Mice.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway plays a pivotal role in abdominal aortic aneurysm (AAA). However, systemic inhibition of this pathway causes serious side effects, thus limiting the clinical use of pan-PI3K inhibitors. In this study, it was hypothesised that the γ subunit of PI3K plays an important role in the PI3K/AKT signalling pathway during AAA, and that specifically targeting PI3Kγ may prevent this process. METHODS: Aortic specimens were collected from AAA patients and organ donors. Furthermore, a classical AAA model in male C57BL/6 mice was created via an intra-aortic porcine pancreatic elastase (PPE) infusion and aortas were collected. A specific PI3Kγ inhibitor, IPI-549, was administered to mice orally. The protein expression level of PI3Kγ was examined by immunohistochemistry and western blotting. The aortic leukocytes were examined by immunohistochemistry and flow cytometry. RESULTS: PI3Kγ protein levels were elevated in the aortas of AAA patients and PPE infused mice. Three color immunofluorescence staining revealed the predominant area of PI3Kγ by T cells and macrophages in aneurysmal aortas. IPI-549 treatment significantly prevented AAA formation in mice. Aortic macrophages, T cells and neo-angiogenesis were significantly reduced in mice treated with IPI-549 compared with vehicle treated PPE infused mice. Flow cytometry analysis also revealed that CD45+ leukocytes and CD45+ F4/80+ macrophages in IPI-549 treated mouse aortas decreased dramatically. Additionally, IPI-549 treatment inhibited the phosphorylation of AKT in experimental aneurysmal lesions. CONCLUSION: Specific inhibition of PI3Kγ limits AAA formation. Targeting PI3Kγ prevents inflammatory cell infiltration through inhibition of AKT phosphorylation in AAA.

Spermidine Suppresses Development of Experimental Abdominal Aortic Aneurysms.

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 AAAs were induced in 8- to 10-week-old male C57BL/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 AAAs 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 SQSTM1/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.