ABSTRACT
Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease that currently lacks effective pharmacological treatment given the complex pathophysiology of the disease. Here, single-cell RNA-sequencing data from patients with AAA and a mouse model are analyzed, which reveals pivotal pathological changes, including the M1-like polarization of macrophages and the loss of contractile function in smooth muscle cells (SMCs). Both cell types express the integrin αvß3, allowing for their dual targeting with a single rationally designed molecule. To this end, a biocompatible nanodrug, which is termed EVMS@R-HNC, that consists of the multifunctional drug everolimus (EVMS) encapsulated by the hepatitis B virus core protein modifies to contain the RGD sequence to specifically bind to integrin αvß3 is designed. Both in vitro and in vivo results show that EVMS@R-HNC can target macrophages as well as SMCs. Upon binding of the nanodrug, the EVMS is released intracellularly where it exhibits multiple functions, including inhibiting M1 macrophage polarization, thereby suppressing the self-propagating inflammatory cascade and immune microenvironment imbalance, while preserving the normal contractile function of SMCs. Collectively, these results suggest that EVMS@R-HNC presents a highly promising therapeutic approach for the management of AAA.
ABSTRACT
Background: Currently, the optimal technique to revascularize the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) remains controversial. Our study seeks to characterize early and late clinical results and to assess the advantages and disadvantages of endovascular vs. surgical strategies for the preservation of LSA. Methods: PubMed, Embase and Cochrane Library searches were conducted under the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) standards. Only literature published after January 1994 was included. Studies reporting on endovascular revascularization (ER), surgical revascularization (SR) for LSA preservation were included. 30-day mortality and morbidity rates, restenosis rates, and rates of early and late reintervention are measured as outcomes. Results: A total of 28 studies involving 2,759 patients were reviewed. All articles were retrospective in design. Single-arm analysis found no significant statistical differences in ER vs. SR in terms of 30-day mortality and perioperative complication rates. The mean follow-up time for the ER cohort was 12.9 months and for the SR cohort was 26.6 months, respectively. Subgroup analysis revealed a higher risk of perioperative stroke (4.2%) and endoleaks (14.2%) with the chimney technique compared to the fenestrated and single-branched stent approaches. Analysis of the double-arm studies did not yield statistically significant results. Conclusion: Both ER and SR are safe and feasible in the preservation of LSA while achieving an adequate proximal landing zone. Among ER strategies, the chimney technique may presents a greater risk of neurological complications and endoleaks, while the single-branched stent grafts demonstrate the lowest complication rate, and the fenestration method for revascularization lies in an intermediate position. Given that the data quality of the included studies were relatively not satisfactory, more randomized controlled trials (RCTs) are needed to provide convincing evidence for optimal approaches to LSA revascularization in the future.
ABSTRACT
Objective: This study aims to assess the suitability of four types of commercial iliac branch device systems to treat Eastern Asian abdominal aortic aneurysm (AAA) patients with bilateral or unilateral common iliac artery aneurysms (CIAAs). Methods: Patients with a coexisting AAA and a unilateral or bilateral CIAAs who underwent endovascular aneurysm repair (EVAR) at two tertiary centers in China from 2015 to 2017 were reviewed. Morphology of lesions was measured and the anatomic suitability for Cook iliac branch device (IBD), Gore iliac branch endoprosthesis (IBE), Lifetech iliac branch stent graft (IBSG), and Jotec IBD was evaluated according to the latest instructions for use. Results: Seventy-six patients with AAA were enrolled, including 35 bilateral CIAAs, 41 unilateral CIAAs. A hundred and eleven lesions were investigated aggregately: 16.2, 28.8, 21.6, and 19.8% met the criteria for Cook IBD, Gore IBE, Lifetech IBSG, and Jotec IBD, respectively. A total of 34 (44.7%) patients could be treated for at least one lateral lesion. The diameter of the internal iliac artery (IIA) was the most common restriction for IBD application. Additionally, the IIA diameter of lesions in the bilateral group was significantly larger compared with the unilateral group (P < 0.001). Based on the anatomical characteristics alone, it is likely that IBDs will be more suitable for unilateral lesions than bilateral ones (P < 0.05). However, there was no difference between the suitability for patients with unilateral or bilateral CIAAs (P > 0.05). Conclusions: Less than half of Eastern Asian patients with aortoiliac aneurysms were eligible for IBD application. This was primarily due to the IIA diameter failing to meet the criteria. And thus, the suitability of lesions in bilateral group was significantly lower than that in the unilateral group. Aiming to expand the indications and optimize the design of the iliac branch devices, IIA diameter and the anatomical characteristics of the bilateral lesions should be considered deliberately.
ABSTRACT
AIMS: This study aims to investigate the effects of intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) on a thin-endometrium rat model. MAIN METHODS: Twenty rats in two groups of 10 were used. Group I was perfused with normal saline (NS) in the right uterine horn and 95% ethanol in the left one. Group II was bilaterally perfused with 95% ethanol into the uterine horns. After three estrous cycles, Group II was perfused with NS in the right uterine horn and G-CSF (30 µg/kg) in the left one. Hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining were used to detect changes in endometrial thickness and expression of cytokeratin 19 (CK19) and vimentin (Vim). The relative expression levels of vascular endothelial growth factor (Vegf) and leukemia inhibitory factor (Lif) were also tested via reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and Western-blot analyses. KEY FINDINGS: G-CSF treatment significantly increased the thickness of the endometrium in the 95% ethanol-induced thin-endometrium rat model. The expression levels of endometrial glandular epithelial cell marker for CK19 and stromal cell marker Vim were augmented in the G-CSF-treated group compared with the control group. Moreover, G-CSF treatment stimulated the expression of VEGF and LIF in the 95% ethanol-induced thin-endometrium rat model. SIGNIFICANCE: G-CSF intrauterine perfusion improved endometrial receptivity in the thin-endometrium rat model by stimulating endometrial proliferation and angiogenesis.
