Background Preclinical studies have suggested that adipose-derived mesenchymal stem cells (ADSCs) transplantation can suppress abdominal aortic inflammation and aneurysm expansion through paracrine factors. Yet, the mechanism of action is not fully understood. In the present study, we further examined the function and mechanism of ADSC-derived exosomes (ADSC-exos) and their microRNA-17-5p (miR-17-5p) on the abdominal aortic aneurysm (AAA) progression. Methods ADSC-exos were isolated and identified. DiR and PKH67 staining were used to trace ADSC-exo in vivo and in vitro. Raw264.7 cells were applied to perform in vitro experiments, while a murine AAA model induced using angiotensin II (Ang II) was used for in vivo testing. The expression level of miR-17-5p in macrophages and Ang II-treated macrophages after ADSC-exos treatment was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The target relation between miR-17-5p and thioredoxin-interacting protein (TXNIP) was identified by a dual-luciferase reporter gene assay. Artificial activation and block of experiments of miR-17-5p and TXNIP were conducted to clarify their functions in inflammation during AAA progression. The severity of AAA between groups was assessed by maximal aorta diameter, AAA incidence, survival rate, and histological stainings. Besides, inflammasome-related proteins and macrophage pyroptosis were further evaluated using western blot, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Results The ADSC-exos were isolated and identified. In vivo testing showed that ADSC-exos were mainly distributed in the liver. Meanwhile, in vitro experiments suggested that ADSC-derived exosomes were taken up by macrophages, while inside, ADSC-exos miR-17-5p decreased a TXNIP induced by Ang II by directly binding to its 3′-untranslated region (3’UTR). Furthermore, overexpression of miR-17-5p enhanced the therapeutic function of ADSC-exos on inflammation during AAA expansion in vivo, while its inhibition reversed this process. Finally, overexpressed TXNIP triggered macrophage pyroptosis and was alleviated by ADSC-derived exosomes in vitro. Conclusion ADSC-exos miR-17-5p regulated AAA progression and inflammation via the TXNIP-NLRP3 signaling pathway, thus providing a novel insight in AAA treatment.
BackgroundThromboangiitis obliterans (TAO, Buerger's disease) is an inflammatory and obstructive vasculopathy, which leads to limb ischemic rest pain and ulcerations in the acute stage.ObjectivesThis study aimed to assess the feasibility of excimer laser-assisted balloon angioplasty (BA) for patients with acute infrapopliteal TAO.MethodThis was a single-center retrospective cohort study. In this study, 220 patients with 210 target limbs between January 2012 and September 2021 were involved. Among them, 52 target limbs have received endovascular excimer laser-assisted balloon angioplasty from January 2017. The ankle brachial index (ABI), rest pain score, ulcer, Rutherford classification, and TASC II classification were assessed. The follow-up time was 6 months.ResultsThe technical success rate of laser + BA and BA groups was 71.15 and 65.82% (p = 0.5021), respectively. After intervention, the ABI of two groups were 0.85 ± 0.20 and 0.77 ± 0.20 (p = 0.0419), and the rest pain score was 1.00 ± 1.43 and 1.71 ± 2.25 (p = 0.0449). During the 6 months follow-up, the ABI of two groups was 0.76 ± 0.17 and 0.75 ± 0.23 (p = 0.8539), the rest pain score was 1.43 ± 1.82 and 2.24 ± 2.06 (p = 0.0783), and the ulcer rate was 23.68 and 40.98% (p = 0.0867), respectively. The proportion of patients who were assessed as TASC II C/D or Rutherford 4–6 in laser +BA group was significantly lower than that in BA group, indicating that the former had better efficacy. The rate of critical limb ischemia and restenosis in the laser +BA group was lower than that in the BA group (47.36 vs. 67.22%; 21.05 vs. 34.43%) during follow-up. In the laser + BA group, the reintervention rate was lower than that in the BA group (2.70 vs. 8.20%, p = 0.0425). No serious adverse events (AEs) occurred.ConclusionExcimer laser debulking-assisted angioplasty is a feasible, effective, and safe method to treat acute infrapopliteal TAO.
Endovascular interventions, such as balloon dilation and stent implantation, are currently recommended as the primary treatment for patients with peripheral artery disease (PAD), greatly improving patient prognosis. However, the consequent lumen restenosis that occurs after endovascular interventions has become an important clinical problem. Inflammation has been proven to be crucial to postoperative restenosis. In previous studies we have identified that Netrin-1-modified adipose-derived stem cells (N-ADSCs) transplantation is an effective anti-inflammatory strategy to repair vascular damage. Nevertheless, it remained to be explored how one could constantly deliver N-ADSCs onto damaged arteries. Therefore, we developed an adhesive double network (DN) hydrogel wrap loaded with N-ADSCs for sustained perivascular delivery. Inspired by the adhesion mechanism of mussels, we developed an adhesive and tough polyacrylamide/calcium-alginate/reduced graphene oxide/polydopamine (PAM/CA/rGO/PDA) hydrogel. Dopamine was attached to graphene sheets and limitedly oxidized to generate free catechol groups. The hydrogel could wrap damaged arteries and induce anti-inflammatory effects through N-ADSCs. In vitro experiments demonstrated that N-ADSCs significantly promoted the M2 polarization of macrophages to anti-inflammatory phenotypes and reduced the expression of inflammatory factors. In vivo experiments in a rat carotid artery guidewire injury model showed that the adhesive hydrogel wrap loaded with N-ADSCs could significantly reduce arterial inflammation, inhibit intimal hyperplasia and improve re-endothelialization. Altogether, this newly developed N-ADSCs-loaded hydrogel wrap provides an effective slow-releasing system, which may be a promising way to prevent and treat restenosis after endovascular interventions.
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