NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4-ANXA2 Interaction and Enhancing Macrophage Infiltration.

Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury-induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)-induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2-Cre mice on an ApoE-/- background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro-inflammatory responses. Bulk RNA-sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF-κB/CCR2 signaling pathway. Protein-protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro-inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

Drug-coated balloon therapy for in-stent restenosis in patients with iliofemoral deep vein thrombosis: A single-arm observational study.

BACKGROUND: Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in-stent restenosis (ISR) has become an emerging non-negligible problem. METHODS: To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug-coated balloon (DCB) on venous ISR lesions, we conducted a single-center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel-coated balloon dilatation. RESULTS: We found a collagen-rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow-up (p < 0.0001). During follow-up, the VEINES-QOL scores (p < 0.0001), VEINES-Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed. CONCLUSIONS: The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.

Covered Stents vs Bare Metal Stents for Aortoiliac Arterial Diseases: A Systematic Review and Meta-Analysis.

PURPOSE: Covered stents and bare metal stents (BMS) have been regarded as viable treatment options for aortoiliac arterial diseases. We performed this systematic review and meta-analysis to compare the efficacy of covered stents with BMS for aortoiliac arterial diseases. MATERIALS AND METHODS: The Cochrane Library, Embase, and Medline databases were searched by 2 authors (C.Z. and Z.W.) to retrieve all studies comparing the outcomes of covered stents vs BMS for aortoiliac arterial diseases. The Cochrane tool and the Newcastle-Ottawa scale were used to assess the risk of bias in randomized controlled trials and observational studies, respectively. The outcomes at the same stage reported in at least 2 studies were pooled together. The fixed effects model combined the data when I2<50%, otherwise the random effects model was applied. The results for dichotomous variables were presented as odds ratio (OR) or risk difference and 95% confidence interval (CI); continuous variables were reported as mean difference and 95% CI. RESULTS: Herein, 10 studies with a total of 1695 limbs were included. The covered stents significantly increased the freedom from target lesion revascularization (OR 2.85, 95% CI: 1.28-6.33, p=0.010) compared to the BMS during a 24-month follow-up. However, no statistically significant difference was found in the technical success, primary patency, secondary patency, major adverse events (MAEs), ankle-brachial index (ABI) improvement, limb salvage, and survival between the two groups. CONCLUSION: Compared to BMS, covered stents appear to have similar technical success, primary patency, secondary patency, MAEs, ABI improvement, limb salvage, and survival but may have advantages in reducing target lesion revascularization. More well-designed, prospective studies are warranted to determine such findings. CLINICAL IMPACT: Covered stents may increase freedom from target lesion revascularization (TLR) compared to bare metal stents (BMS) in the treatment of aortoiliac arterial diseases. However, technical success, primary patency, secondary patency, major adverse events (MAEs), ABI improvement, limb salvage, and survival were similar. The aforementioned results are still not sufficient to draw a solid conclusion about the selection of stents for aortoiliac arterial diseases. More well-designed, prospective studies are warranted to determine such findings.