A novel Nanocellulose-Gelatin-AS-IV external stent resists EndMT by activating autophagy to prevent restenosis of grafts

Chu, Tianshu; Li, Qingye; Dai, Chun Ling; Li, Xiang; Kong, Xiang; Fan, Yangyang; Yin, Hongyan; Ge, Jianjun

doi:10.1016/j.bioactmat.2022.10.013

Cited by 6 publications

(6 citation statements)

References 94 publications

(102 reference statements)

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“…Considering their convenience and practicality for clinical applications, extravascular scaffolds made of light-cured hydrogels are a promising therapeutic option. Hydrogel scaffolds loaded with traditional Chinese herbs, such as Bletilla and Astragalus membranaceus , have also been reported for the treatment of the restenosis of grafts, and good progress has been made ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Exosomes from umbilical cord-derived mesenchymal stem cells combined with gelatin methacryloyl inhibit vein graft restenosis by enhancing endothelial functions

Deng,

Li,

Chu

et al. 2023

J Nanobiotechnol

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Background The prevalence of coronary artery disease is increasing. As a common treatment method, coronary artery bypass transplantation surgery can improve heart problems while also causing corresponding complications. Venous graft restenosis is one of the most critical and intractable complications. Stem cell-derived exosomes could have therapeutic promise and value. However, as exosomes alone are prone to inactivation and easy removal, this therapeutic method has not been widely used in clinical practice. Methacrylated gelatin (GelMA) is a polymer with a loose porous structure that maintains the biological activity of the exosome and can control its slow release in vivo. In this study, we combined human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and GelMA to explore their effects and underlying mechanisms in inhibiting venous graft restenosis. Results Human umbilical cord mesenchymal stem cells (hUCMSCs) were appraised using flow cytometry. hUCMSC-Exos were evaluated via transmission electron microscopy and western blotting. hUCMSC-Exos embedded in a photosensitive GelMA hydrogel (GelMA-Exos) were applied topically around venous grafts in a rat model of cervical arteriovenous transplantation, and their effects on graft reendothelialization and restenosis were evaluated through ultrasonic, histological, and immunofluorescence examinations. Additionally, we analyzed the material properties, cellular reactions, and biocompatibility of the hydrogels. We further demonstrated that the topical application of GelMA-Exos could accelerate reendothelialization after autologous vein transplantation and reduce restenosis in the rat model. Notably, GelMA-Exos caused neither damage to major organs in mice nor excessive immune rejection. The uptake of GelMA-Exos by endothelial cells stimulated cell proliferation and migration in vitro. A bioinformatic analysis of existing databases revealed that various cell proliferation and apoptosis pathways, including the mammalian target of rapamycin (mTOR)–phosphoinositide 3-kinase (PI3K)–AKT signaling pathways, might participate in the underlying regulatory mechanism. Conclusions Compared with the tail vein injection of hUCMSC-Exos, the local application of a mixture of hUCMSC-Exos and GelMA was more effective in promoting endothelial repair of the vein graft and inhibiting restenosis. Therefore, the proposed biomaterial-based therapeutic approach is a promising treatment for venous graft restenosis.

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Section: Discussionmentioning

confidence: 99%

Exosomes from umbilical cord-derived mesenchymal stem cells combined with gelatin methacryloyl inhibit vein graft restenosis by enhancing endothelial functions

Deng,

Li,

Chu

et al. 2023

J Nanobiotechnol

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“…It was established that 51.7%±3.3% (mean ± SEM) of neointimal cells were of endothelial origin and that EndMT is a central component of neointimal hyperplasia in mice ( 6 ). In the process of EndMT, endothelial cells lose cell-cell junctions and acquire a mesenchymal cell-like phenotype ( 1 , 2 ). A growing body of evidence supports the importance of TGF-β signaling in EndMT ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their specific markers and acquire mesenchymal or myofibroblastic phenotypes ( 1 , 2 ). Many studies, including our previous research, have verified that vascular smooth muscle cells (VSMCs) play a key role in the process of neointimal hyperplasia ( 3 - 5 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of endothelial-to-mesenchymal transition by histone deacetylase 3 posttranslational modifications in neointimal hyperplasia

Chen¹,

He²,

Zhang³

et al. 2023

Ann Transl Med

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Background Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their specific markers and acquire mesenchymal or myofibroblastic phenotypes. Studies have demonstrated the importance of endothelial-derived vascular smooth muscle cells (VSMCs) through EndMT in neointimal hyperplasia. Histone deacetylases (HDACs) are epigenetic modification enzymes involved in the epigenetic control of important cellular functions. Recent studies found that HDAC3, a class I HDAC, causes posttranslational modifications, including deacetylation and decrotonylation. However, the effect of HDAC3 on EndMT in neointimal hyperplasia via posttranslational modifications remains to be seen. Therefore, we investigated the effects of HDAC3 on EndMT in carotid artery-ligated mice and human umbilical vein endothelial cells (HUVECs) and the underlying posttranslational modifications. Methods HUVECs were treated with transforming growth factor (TGF)-β1 or the inflammatory cytokine tumor necrosis factor (TNF)-α at different concentrations and durations. In HUVECs, HDAC3 expression, the expression of endothelial and mesenchymal markers, and posttranslational modifications were analyzed with Western blotting, quantitative real-time polymerase chain reaction (PCR), and immunofluorescence. C57BL/6 mice underwent left carotid artery ligation. Mice were treated with the HDAC3-selective inhibitor RGFP966 (10 mg/kg, i.p.) from 1 day before to 14 days after ligation. Then, the sections of the carotid arteries were examined histologically using hematoxylin and eosin (HE) and immunofluorescence staining. The carotid arteries from other mice were examined for the expression of EndMT markers and inflammatory cytokines. Furthermore, the acetylation and crotonylation of carotid arteries were immunostained in mice. Results In HUVECs, TGF-β1 and TNF-α induced EndMT by decreasing CD31 expression and increasing α-smooth muscle actin expression. TGF-β1 and TNF-α also upregulated HDAC3 expression in HUVECs. The in vivo study in mice indicated that RGFP966 significantly alleviated neointimal hyperplasia of the carotid artery compared with vehicle treatment. Furthermore, RGFP966 suppressed EndMT and the inflammatory response in carotid artery-ligated mice. Further investigation revealed that HDAC3 regulated EndMT by posttranslational modifications of deacetylation and decrotonylation. Conclusions These results suggest that HDAC3 regulates EndMT in neointimal hyperplasia through posttranslational modifications.

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“…Its chemical structure is composed of a tetracyclic triterpene alcohol backbone and a sugar group. Additionally, Astragaloside IV contains multiple hydroxyl and sugar groups, which can stabilize free radicals through reaction, thereby reducing oxidation reactions [10].…”

Section: Radix Astragali (Astragalus Membranaceus (Fisch) Bunge)mentioning

confidence: 99%

Traditional herbs: mechanisms to combat cellular senescence

Wang,

Yang

et al. 2023

Aging

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Cellular senescence plays a very important role in the ageing of organisms and age-related diseases that increase with age, a process that involves physiological, structural, biochemical and molecular changes in cells. In recent years, it has been found that the active ingredients of herbs and their natural products can prevent and control cellular senescence by affecting telomerase activity, oxidative stress response, autophagy, mitochondrial disorders, DNA damage, inflammatory response, metabolism, intestinal flora, and other factors. In this paper, we review the research information on the prevention and control of cellular senescence in Chinese herbal medicine through computer searches of PubMed, Web of Science, Science Direct and CNKI databases.

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A novel Nanocellulose-Gelatin-AS-IV external stent resists EndMT by activating autophagy to prevent restenosis of grafts

Cited by 6 publications

References 94 publications

Exosomes from umbilical cord-derived mesenchymal stem cells combined with gelatin methacryloyl inhibit vein graft restenosis by enhancing endothelial functions

Exosomes from umbilical cord-derived mesenchymal stem cells combined with gelatin methacryloyl inhibit vein graft restenosis by enhancing endothelial functions

Regulation of endothelial-to-mesenchymal transition by histone deacetylase 3 posttranslational modifications in neointimal hyperplasia

Traditional herbs: mechanisms to combat cellular senescence

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