TNFα activation and TGFß blockage act synergistically for smooth muscle cell calcification in patients with venous thrombosis via TGFß/ERK pathway.

Venous calcification has been observed in post-thrombotic syndrome (PTS) patients; yet, the cell types and possible mechanisms regulating this process are still unclear. We evaluated the calcium deposition within the venous wall, the cell type involved in the calcified remodelling of the venous wall after thrombosis and explored possible mechanisms in vitro. Calcium deposition was found in human specimens of superficial thrombotic veins and was co-localized with VSMCs markers αSMA and TAGLN (also known as SM22α). Besides, the expression of osteogenesis-related genes was dramatically changed in superficial thrombotic veins. Moreover, the inhibition of the TGFß signalling pathway after TNFα treatment effectively induced the expression of osteogenic phenotype markers, the calcium salt deposits and the obvious phosphorylation of ERK1/2 and JNK2 in the VSMCs calcification model. Supplementing TGFß2 or blocking the activation of the ERK/MAPK signalling pathway prevented the transformation of VSMCs into osteoblast-like cells in vitro. Taken together, VSMCs have an important role in venous calcification after thrombosis. Supplementing TGFß2 or inhibiting the ERK/MAPK signalling pathway can reduce the appearance of VSMCs osteogenic phenotype. Our findings may present a novel therapeutic approach to prevent of vascular calcification after venous thrombosis.

Comparing Safety and Efficacy of Rivaroxaban with Warfarin for Patients after Successful Stent Placement for Chronic Iliofemoral Occlusion: A Retrospective Single Institution Study.

OBJECTIVE: The aim was to compare the safety and effectiveness of rivaroxaban and warfarin as anticoagulants for treating patients with post-thrombotic syndrome (PTS) with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting. METHODS: This single institution retrospective study analysed patients with PTS with chronic iliofemoral venous occlusion who were prescribed rivaroxaban or warfarin for one year after successfully undergoing iliofemoral venous stenting. The primary safety and efficacy endpoints were bleeding complication rate and primary patency rate at one year. Secondary outcomes included Villalta score, symptom recurrence rate, ulcer healing rate, and clinically driven target lesion revascularisation (CD-TLR) rate during follow up. RESULTS: From January 2016 to December 2017, 154 legs from 154 patients were included in this study (69 in rivaroxaban group and 85 in warfarin group). The groups were well matched for patient demographics, clinical characteristics, and procedural details. There was no significant difference between the rivaroxaban group and warfarin group in bleeding complication rate (10% vs. 16%, p = .23, hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.25 - 1.37) at one year, as well as major bleeding complication rate (0% vs. 2%, p = .20, HR 0.16, 95% CI 0.01 - 2.61) and minor bleeding complication rate (10% vs. 14%, p = .40, HR 0.67, 95% CI 0.27 - 1.66). The primary patency rate was higher in the rivaroxaban group at one year (84% vs. 71%, p = .049, HR 0.50, 95% CI 0.26 - 0.96) and at two years (79% vs. 63%, p = .037, HR 0.52, 95% CI 0.29 - 0.93). At a mean follow up of 24 months (range 1 - 42 months), the rivaroxaban group had a significantly lower post-operative Villalta score (4.87 ± 3.51 vs. 6.88 ± 5.85, p = .010, t = 2.64, 95% CI 0.50 - 3.52), lower rate of symptom recurrence (4% vs. 32%, p < .001), lower CD-TLR rates (3% vs. 13%, p = .039), and higher ulcer healing rate (90% vs. 59%, p = .004) than the warfarin group. CONCLUSION: For PTS patients with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting, rivaroxaban probably exhibited similar safety but superior efficacy to warfarin. However, further prospective control studies with large sample size are necessary to confirm the results.

Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease.

Inflammatory macrophage (Mφ)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mφ-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mφ and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mφ in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.

Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages.

Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases.

An effective approach to reduce inflammation and stenosis in carotid artery: polypyrrole nanoparticle-based photothermal therapy.

Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE(-/-) mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.

Photothermal theragnosis synergistic therapy based on bimetal sulphide nanocrystals rather than nanocomposites.

A new generation of photothermal theranostic agents is developed based on Cu3BiS3 nanocrystals. A computed tomography imaging response and photothermal effect, as well as near-infrared fluorescence emission, can be simultaneously achieved through Cu3BiS3 nanocrystals rather than frequently used nanocomposites. These results provide some insight into the synergistic effect from bimetal sulphide semiconductor compounds for photothermal theragnosis therapy.