Abdominal aortic aneurysm (AAA) is a chronic dilated disease of the aorta that is characterized by chronic inflammation. Curcumin (Cur) is previously showed to attenuate AAA by inhibiting inflammatory response in ApoE −/− mice. Since Cur has the limitations of aqueous solubility and instability. Here, we focus on the role of curcumin nicotinate (CurTn), a Cur derivative is derived from Cur and nicotinate. An in vitro model of AAA was established by treating vascular smooth muscle cells (VSMCs) with II (Ang-II). Gene and protein expressions were examined by quantitative real-time PCR (qPCR) or western blotting. Cell migration and pyroptosis were determined by transwell assay and flow cytometry. The interaction between plasmacytoma variant translocation 1 (PVT1), miR-26a and krüppel-like factor 4 (KLF4) was predicted by online prediction tool and confirmed by luciferase reporter assay. CurTn reduced Ang-II-induced AAA-associated proteins, inflammatory cytokine expressions, and attenuated pyroptosis in VSMCs. PVT1 overexpression suppressed the inhibitory effect of CurTn on AngII-induced pyroptosis and inflammatory in VSMCs by sponging miR-26a. miR-26a directly targeted KLF4 and suppressed its expression, which eventually led to the deactivation of the PI3K/AKT signaling pathway. Besides, the regulatory effect of CurTn on pyroptosis of VSMCs induced by Ang-II was reversed through the PVT1/miR-26a/KLF4 pathway. In short, CurTn suppressed VSMCs pyroptosis and inflammation though mediation PVT1/miR-26a/KLF4 axis by regulating the PI3K/AKT signaling pathway, CurTn might consider as a potential therapeutic target in the treatment of AAA.
Background Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular abnormality, that, if ruptured, is almost universally fatal without repair, and is associated with up to 50% mortality even if repaired in hospital. To date, there is no drug therapy that has clinically proven benefit to reduce or prevent expansion of AAA. The aim of this study was to investigate whether Daxx could affect AAA through inhibiting the PI3K/AKT/ID2 signaling pathway mediated by transforming growth factor β-1 (TGFβ1). Methods The AAA model was constructed by injecting angiotensin Ⅱ (Ang-Ⅱ) into rats, and the Daxx lentivirus vector was constructed. Hematoxylin and eosin (HE) staining was used to detect the wall thickness of the abdominal aorta in rats. The gene and protein expressions in abdominal aortic tissues were detected utilizing western blot, immunohistochemistry (IHC) and fluorescence quantitative real-time polymerase chain reaction (qRT-PCR). Finally, the concentration of TGF-β1 in abdominal aortic tissue was determined by ELISA. Results The abdominal aortic wall thickness was decreased in the Daxx expression group (by HE staining), and Daxx overexpression markedly reduced the protein expression levels of MMP2 and MMP9. Proteins related to the PI3K/AKT/ID2 signaling pathway were highly enhanced in the aneurysm wall of rats, but were reduced following Daxx addition. Moreover, Daxx reduced the damage to elastin (by IHC), and the expression levels of α-SMA and SM22α were up-regulated by Daxx (by qRT-PCR). The concentration of TGF-β1 was correlated with the activation of the PI3K/AKT/ID2 signaling pathway (by ELISA), whereas AKT overexpression weakened the inhibitory effect of Daxx. Conclusion Daxx ameliorated several mechanisms that contributed to expansion of AAA suppressing the tissue concentration of TGF-β1, thereby inhibiting the activation of the PI3K/AKT/ID2 signaling pathway. This evidence might form the basis to develop a therapeutic target for AAA.
Objective The objective is to investigate whether percutaneous access (pEVAR) is superior to cutdown access (cEVAR) in terms of safety and efficacy during endovascular repair of abdominal aortic aneurysms (AAAs). Methods We searched PubMed, Embase, and Cochrane Library from January 1999 to December 2020 for studies reporting on the comparison between percutaneous and cutdown techniques for endovascular repair of AAAs. Outcomes evaluated were technical success rates, access site-related complications and operative time, and hospital stay. Results Four randomized controlled trials and nine observational studies with a total of 1683 patients comprising 2715 groin accesses were eligible for the meta-analysis. pEVAR was associated with a lower risk of overall complications (odds ratio (OR) = 0.63; p = .005) and seroma/lymphorrhea (OR, 0.18; p = .0001) and shortened operation time (MD = −39.04; p = .002) and the length of hospital stay (MD = −0.75; p < .00001) compared with cEVAR. The technical success rate for pEVAR was 95.1% (694/729), with an overall OR of 0.27 (95% CI 0.14–0.55, p = .0003) comparing pEVAR with cEVAR. Furthermore, pEVAR did not increase the risk of site infection, femoral artery thrombosis, postoperative hematoma, nerve injury, dissection, and bleeding. Conclusion Percutaneous endovascular aneurysm repair is a safe and effective method for the treatment of AAA. It reduces the risk of overall complications and shortens the operation time and hospital stay. The technical success rate of pEVAR is lower than that of cEVAR, which may be linked to the selection of patients, operator experience, and the use of ultrasound. Large definitive trials are required to draw robust conclusions.
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