Fibulin-1 promotes intimal hyperplasia after venous stent implantation through ACE mediated angiotensin II signaling.

Objective: Stent intimal hyperplasia leads to in stent restenosis and thrombosis. This study determined whether Fibulin-1 activity in smooth muscle cells (SMCs) contributes to stent restenosis or thrombosis. Methods: Stent implantation was conducted in a pig model. Target vessel samples were stained and analyzed by protein mass spectrometry. Cell experiments and Fibulin-1 SMC specific knockout mice (Fbln1SMKO) were used to investigate the mechanism of Fibulin-1 induced SMC proliferation and thrombosis. Results: SMC proliferation and phenotypic transition are the main pathological changes of intimal hyperplasia in venous stents. Protein mass spectrometry analysis revealed a total of 67 upregulated proteins and 39 downregulated proteins in intimal hyperplasia after stent implantation compared with normal iliac vein tissues. Among them, Fibulin-1 ranked among the top proteins altered. Fibulin-1 overexpressing human SMCs (Fibulin-1-hSMCs) showed increased migration and phenotypic switching from contractile to secretory type and Fibulin-1 inhibition decreased the activity of SMCs. Mechanistically, Fibulin-1-hSMCs displayed increased levels of angiotensin converting enzyme (ACE) expression and angiotensin II signaling. Inhibition of ACE or angiotensin II signaling alleviated the migration of Fibulin-1-hSMCs. Using Fibulin-1 SMC specific knockout mice (Fbln1SMKO) and venous thrombosis model, we demonstrated that Fibulin-1 deletion attenuated intimal SMCs proliferation and thrombosis. Further, Fibulin-1 concentration was high in iliac vein compression syndrome (IVCS) patients treated with stent and was an independent predictor of venous insufficiency. Conclusions: Fibulin-1 promotes SMC proliferation partially through ACE secretion and angiotensin II signaling after stent implantation. Fibulin-1 plays a role in venous insufficiency syndrome, implicating the protein in the detection and treatment of IVCS.

TRIM27 Promotes Endothelial Progenitor Cell Apoptosis in Patients with In-Stent Restenosis by Ubiquitinating TBK1.

Approximately 2-10% in-stent restenosis (ISR) may occur following percutaneous coronary intervention (PCI) despite the use of modern drug-eluting stents (DES); thus, our study aimed to explore the effects of tripartite motif-containing (TRIM) 27 on ISR and the underlying mechanism. For this purpose, a total of 42 patients undergoing coronary angiography who had prior coronary angiography with DES implantation were recruited. Endothelial progenitor cells (EPCs) markers (defined as CD34 and vascular endothelial growth factoreceptor-2 (VEGFR-2)) in peripheral blood were measured to asses the circulating EPC level. The TRIM family-related gene expressions were detected by reverse transcription-quantitative polymerase chain reaction. Results suggested that ISR patients had reduced CD34+VEGFR-2+ and increased apoptosis rate of EPCs, along with upregulated TRIM27 and TRIM37 and downregulated TRIM28. TRIM27 promoted and TBK1 inhibited the apoptosis rate of EPCs. Mechanically, TRIM27 interacted with TBK1 to ubiquitinate TBK1 in in vitro study. In summary, TRIM27 promoted the progression of ISR in patients after PCI by ubiquitinating TBK1, which might provide novel ideas for the clinical treatment of ISR.

In-stent Restenosis After Stenting for Superior Mesenteric Artery Dissection Is Associated With Stent Landing Zone: From Clinical Prediction to Hemodynamic Mechanisms.

OBJECTIVE: To identify risk factors for in-stent restenosis (ISR) in patients undergoing stent placement for superior mesenteric artery dissection (SMAD) and to determine the hemodynamic mechanism underlying ISR. METHODS: For this retrospective study, patients with SMAD who had ISR after stent placement were included in the ISR group, and age- and sex-matched patients with SMAD who did not experience ISR after stent placement were included in the control group. Clinical, imaging, and hemodynamic data were assessed. Multivariable regression was used to identify independent ISR risk factors. Structural and fluid dynamics simulations were applied to determine the hemodynamic mechanism underlying the occurrence of ISR. RESULTS: The study population included 26 patients with ISR and 26 control patients. Multivariate analysis demonstrated that stent-to-vascular (S/V) ratio (odds ratio [OR], 1.14; 95% confidence interval [CI]: 1.00-1.29; p=0.045), stent proximal position >10 mm away from the SMA root (OR, 108.67; 95% CI: 3.09-3816.42; p=0.010), and high oscillatory shear index (OSI) area (OR, 1.25; 95% CI: 1.02-1.52; p=0.029) were predictors of ISR. In structural and fluid dynamics simulations, a stent proximal position near the abdominal aorta (AA) or entering into the AA reduced the contact area between the proximal struts of the stent and the vascular wall, and alleviated the distal lumen overdilation. CONCLUSION: The S/V ratio, stent proximal position away from the SMA root (>10 mm), and high OSI area are independent risk factors for ISR in patients with SMAD undergoing stent placement. Deploying the proximal end of the stent near the AA or entering into the AA appears to improve the hemodynamic environment in the SMA lumen and ultimately reduce the risk of ISR. CLINICAL IMPACT: In-stent restenosis is an uncommon but potentially catastrophic complication after stent placement for the management of superior mesenteric artery dissection. This study identified risk factors for in-stent restenosis and demonstrated that, as long as the stent can fully cover the dissection range, deploying the proximal end of the stent near the abdominal aorta or less entering into the abdominal aorta may reduce the risk of in-stent restenosis in this patient population.

Endovascular treatment of symptomatic severe intracranial atherosclerotic stenosis with a novel intracranial dedicated drug-eluting stent: a more effective treatment approach.

Background: Endovascular treatment of severe intracranial atherosclerotic stenosis (ICAS) using coronary drug-eluting stents (DESs) significantly reduces the risk of in-stent restenosis (ISR) and stroke recurrence. However, there are few reports regarding the treatment of ICAS with intracranial dedicated DES. Herein, we present our experience with the feasibility, safety, and medium-term follow-up outcomes of a novel intracranial DES, named NOVA stent, in patients with symptomatic severe ICAS (≥70%). Methods: From December 2021 to May 2022, patients with symptomatic severe ICAS who underwent implantation of the NOVA stent in our institution were retrospectively analyzed for procedural results, perioperative complications, imaging and clinical follow-up outcomes. Results: Twenty-four patients, 16 (66.7%) with anterior circulation lesions and 8 (33.3%) with posterior circulation lesions, were enrolled. All patients with intracranial ICA (n = 6), middle cerebral artery (n = 10), basilar artery (n = 3), intracranial vertebral artery (n = 3), and the vertebrobasilar junction (n = 2) stenosis were treated successfully using NOVA stents. The severity of stenosis ranged from 75 to 96% (mean 85.9%) before treatment and this was reduced to 0 to 20% (mean 8.6%) immediately after stent placement. Symptomatic distal embolism occurred in one case; however, there were no other perioperative complications. The mean follow-up duration was 12.2 ± 1.06 months. No symptomatic ischemic events occurred during follow-up. Follow-up cerebral angiography was performed in 22 of 24 patients (91.7%), and significant ISR occurred in one patient (4.2%). Conclusion: Our results demonstrate that implantation of the novel intracranial DES NOVA in severe ICAS is feasible, safe, and effective in selected cases, reducing the incidence of ISR, and showing excellent midterm clinical outcomes, providing a promising option for ICAS treatment.

Platelet bioenergetic profiling uncovers a metabolic pattern of high dependency on mitochondrial fatty acid oxidation in type 2 diabetic patients who developed in-stent restenosis.

Although platelet bioenergetic dysfunction is evident early in the pathogenesis of diabetic macrovascular complications, the bioenergetic characteristics in type 2 diabetic patients who developed coronary in-stent restenosis (ISR) and their effects on platelet function remain unclear. Here, we performed platelet bioenergetic profiling to characterize the bioenergetic alterations in 28 type 2 diabetic patients with ISR compared with 28 type 2 diabetic patients without ISR (non-ISR) and 28 healthy individuals. Generally, platelets from type 2 diabetic patients with ISR exhibited a specific bioenergetic alteration characterized by high dependency on fatty acid (FA) oxidation, which subsequently induced complex III deficiency, causing decreased mitochondrial respiration, increased mitochondrial oxidant production, and low efficiency of mitochondrial ATP generation. This pattern of bioenergetic dysfunction showed close relationships with both α-granule and dense granule secretion as measured by surface P-selectin expression, ATP release, and profiles of granule cargo proteins in platelet releasates. Importantly, ex vivo reproduction of high dependency on FA oxidation by exposing non-ISR platelets to its agonist mimicked the bioenergetic dysfunction observed in ISR platelets and enhanced platelet secretion, whereas pharmaceutical inhibition of FA oxidation normalized the respiratory and redox states of ISR platelets and diminished platelet secretion. Further, causal mediation analyses identified a strong association between high dependency on FA oxidation and increased angiographical severity of ISR, which was significantly mediated by the status of platelet secretion. Our findings, for the first time, uncover a pattern of bioenergetic dysfunction in ISR and enhance current understanding of the mechanistic link of high dependency on FA oxidation to platelet abnormalities in the context of diabetes.

Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.

The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased NO expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of eNOS and the protein expression of VEGF, p-Akt, and p-ERK1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.

The Exacerbating Effects of the Tumor Necrosis Factor in Cardiovascular Stenosis: Intimal Hyperplasia.

TNF-α functions as a master regulator of inflammation, and it plays a prominent role in several immunological diseases. By promoting important cellular mechanisms, such as cell proliferation, migration, and phenotype switch, TNF-α induces its exacerbating effects, which are the underlying cause of many proliferative diseases such as cancer and cardiovascular disease. TNF-α primarily alters the immune component of the disease, which subsequently affects normal functioning of the cells. Monoclonal antibodies and synthetic drugs that can target TNF-α and impair its effects have been developed and are currently used in the treatment of a few select human diseases. Vascular restenosis is a proliferative disorder that is initiated by immunological mechanisms. In this review, the role of TNF-α in exacerbating restenosis resulting from neointimal hyperplasia, as well as molecular mechanisms and cellular processes affected or induced by TNF-α, are discussed. As TNF-α-targeting drugs are currently not approved for the treatment of restenosis, the summation of the topics discussed here is anticipated to provide information that can emphasize on the use of TNF-α-targeting drug candidates to prevent vascular restenosis.

Research progress of drug eluting balloon in arterial circulatory system.

The arterial circulatory system diseases are common in clinical practice, and their treatment options have been of great interest due to their high morbidity and mortality. Drug-eluting balloons, as a new type of endovascular interventional treatment option, can avoid the long-term implantation of metal stents and is a new type of angioplasty without stents, so drug-eluting balloons have better therapeutic effects in some arterial circulatory diseases and have been initially used in clinical practice. In this review, we first describe the development, process, and mechanism of drug-eluting balloons. Then we summarize the current studies on the application of drug-eluting balloons in coronary artery lesions, in-stent restenosis, and peripheral vascular disease. As well as the technical difficulties and complications in the application of drug-eluting balloons and possible management options, in order to provide ideas and help for future in-depth studies and provide new strategies for the treatment of more arterial system diseases.

ZFP36L1 controls KLF16 mRNA stability in vascular smooth muscle cells during restenosis after vascular injury.

The RNA-binding zinc finger protein 36 (ZFP36) family participates in numerous physiological processes including transition and differentiation through post-transcriptional regulation. ZFP36L1 is a member of the ZFP36 family. This study aimed to evaluate the role of ZFP36L1 in restenosis. We found that the expression of ZFP36L1 was inhibited in VSMC-phenotypic transformation induced by TGF-ß, PDGF-BB, and FBS and also in the rat carotid injury model. In addition, we found that the overexpression of ZFP36L1 inhibited the proliferation and migration of VSMCs and promoted the expression of VSMC contractile genes; whereas ZFP36L1 interference promoted the proliferation and migration of VSMCs and suppressed the expression of contractile genes. Furthermore, the RNA binding protein immunoprecipitation and double luciferase reporter gene experiments shows that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16. Finally, our research results in the rat carotid balloon injury animal model further confirmed that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16 and further plays a role in vascular injury and restenosis in vivo.

Impact of post-procedural peripheral fractional flow reserve after drug-coated balloon angioplasty in femoropopliteal lesions.

PURPOSE: The aim of this study was to determine if postprocedural peripheral fractional flow reserve (pFFR) is associated with patency one year after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) lesions. MATERIALS AND METHODS: Forty-five consecutive patients having 49 de novo FP lesions were enrolled in this prospective, observational study conducted from April 2022 to Aug 2023. The pFFR was measured under hyperemic conditions after the administration of 30 mg of papaverine. The relationship between pFFR and restenosis 12 months after the procedure was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The one-year follow-up was completed for 47 lesions (95.9 %). Restenosis was detected in 7 lesions (14.9 %). Postprocedural pFFR was significantly higher in the nonrestenosis group compared with the pFFR in the stenosis group (0.95 ± 0.054 vs. 0.88 ± 0.090, p = 0.010). The optimal pFFR cutoff value for predicting restenosis was 0.92 (sensitivity, 0.824; specificity, 0.600). The area under the curve for pFFR was numerically higher than the area under the curve for minimum lumen area (0.73 vs. 0.64, p = 0.22). Rates of freedom from restenosis at one year were significantly higher in the pFFR >0.92 group compared with the pFFR ≤0.92 group (p = 0.0042). CONCLUSION: Postprocedural pFFR was associated with patency at one year after DCB angioplasty for FP lesions.

Preoperative sizing to lower in-stent restenosis in peripheral arterial occlusive disease.

OBJECTIVES: The primary treatment for lower extremity peripheral arterial occlusive disease (PAOD) is angioplasty-stenting. Its main complication is in-stent restenosis. Poor selection of stent dimensions has been identified as a factor contributing to early in-stent restenosis. The aim of this study is to determine whether the implantation of stents, selected based on arterial morphological reconstruction using sizing software, reduces the occurrence of in-stent restenosis. The study also aims to evaluate the potential benefits of routine preoperative sizing. METHODS: Between January 2016 and December 2020, all patients treated for PAOD through scheduled angioplasty-stenting in our department were included in the study. Using systematic preoperative Computed Tomography Angiography (CTA), precise reconstruction and sizing were performed to select the ideal length and diameter of stents, resulting in the selection of a so-called IDEAL stent. During the procedure, the surgeon implanted either the IDEAL stent or a different one, named the ACTUAL stent, based on intraoperative data and/or availability. We compared the in-stent restenosis rate between IDEAL and ACTUAL stents. RESULTS: There were no significant differences in the overall characteristics between the IDEAL and ACTUAL stent groups. The in-stent restenosis rate at one year was 13% (N=28/212, P=0.994) in the IDEAL group and 17% (N=25/149, P=0.994) in the ACTUAL group. Among the ACTUAL stents, a total of 19.6% of stents with a diameter mismatch when chosen based on arteriography showed a significantly higher restenosis rate during the first year of follow-up (P=0.02). CONCLUSIONS: Our study did not demonstrate a significant difference in 1-year restenosis rate between the IDEAL and the ACTUAL stents groups. It specifically revealed the significant impact of diameter selection on the intrastent restenosis rate during the first year of follow-up. Stents chosen based on arteriographic criteria, which exhibited diameter discordance, compared to the IDEAL stents group selected using sizing reconstructions, could be either oversized or undersized. This led to a significantly higher restenosis rate at 1 year postoperative.

Outcomes and Comparative Analysis of the Initial Results of Standard Balloon Angioplasty Versus Drug-Coated Balloons Alone Versus in Association With Laser-Excimer Atherectomy in the Treatment of Femoropopliteal Artery In-Stent Restenosis (INTACT).

BACKGROUND: Despite improved patency with newer-generation nitinol stents, one-half of patients will require secondary interventions for in-stent restenosis (ISR). The best treatment strategy remains unclear. This study aimed to compare drug-coated balloons (DCBs) used alone or in association with excimer laser atherectomy (ELA) to simple percutaneous transluminal angioplasty (PTA) in the treatment of femoropopliteal-ISR. METHODS: The INTACT trial is a multicenter, prospective, triple-arm randomized trial conducted across 14 centers from December 2015 to November 2019. Patients Rutherford Class 2-5 with ISR≥70% were followed-up for 18 months. The primary efficacy endpoint was recurrent ISR>70% by duplex ultrasound analysis. The primary safety endpoint was major adverse events (MAEs) defined as death, major amputation, or target lesion revascularization (TLR). RESULTS: Around 134 subjects were randomized to PTA alone (n=41), PTA+DCB (n=43) or PTA+ELA+DCB (n=50). Procedural success was similar (p=.74), as was clinical success (p=.17). The number of recurrent ISR>70% decreased after PTA+ELA+DCB (30.0%; p=.04) and PTA+DCB (30.2%; p=.05) compared to PTA alone (51.2%). Primary patency was higher after PTA+ELA+DCB (log-rank p=.04) and PTA+DCB (log-rank p=.02) compared to PTA alone at 12 months (78.7% and 70.4% vs 61.5%) and 18 months (61.6% and 67.7% vs 37.3%). Freedom from MAEs was lower after PTA+DCB (27.9%) compared to PTA alone (53.7%; p=.02) but did not differ with PTA+ELA+DCB (40.0%). It was primarily driven by TLR; 2 major amputations occurred after PTA+ELA+DCB (4.0%; p=.18). CONCLUSION: This independent study demonstrated a decrease in recurrent ISR>70% and increase in primary patency up to 18 months after PTA+ELA+DCB and PTA+DCB compared to PTA alone in the treatment of FP-ISR. It did not show an increase in MAEs but could have lacked power. CLINICAL IMPACT: This multicenter, prospective, triple-arm randomized, controlled trial focuses on the results of adjunctive therapies, such as excimer laser atherectomy (ELA) and/or drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR) in femoropopliteal lesions in 134 patients. It has the originality of being an independent study funded by a grant from the French Ministry of Health. This study confirms a significant decrease in recurrent ISR >70% and increase in primary patency up to 18 months after the use of ELA+DCB and DCBs compared to simple percutaneous transluminal angioplasty in the treatment of femoropopliteal ISR without an increase in major adverse events.

KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter.

Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

Comparative efficacy of interventional therapies and devices for coronary in-stent restenosis: A systematic review and network meta-analysis of randomized controlled trials.

Background: In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR. Methods: In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308. Results: We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects. Conclusions: DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.

SNHG18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.

AIMS: Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation. METHODS AND RESULTS: Analysis of single cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFß1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs, and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries. CONCLUSION: We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.

Isoxanthohumol reduces neointimal hyperplasia through the apelin/AKT pathway.

The abnormal proliferation, migration, and inflammation of vascular smooth muscle cells (VSMCs) play crucial roles in the development of neointimal hyperplasia and restenosis. Exposure to inflammatory cytokines such as platelet-derived growth factor (PDGF)-BB and tumour necrosis factor-alpha (TNF-α) induces the transformation of contractile VSMCs into abnormal synthetic VSMCs. Isoxanthohumol (IXN) has significant anti-inflammatory, antiproliferative, and antimigratory effects. This study aimed to explore the therapeutic impact and regulatory mechanism of IXN in treating neointimal hyperplasia. The present findings indicate that IXN effectively hinders the abnormal proliferation, migration, and inflammation of VSMCs triggered by PDGF or TNF-α. This inhibition is primarily achieved through the modulation of the apelin/AKT or AKT pathway, respectively. In an in vivo model, IXN effectively reduced neointimal hyperplasia in denuded femoral arteries. These results suggest that IXN holds promise as a potential and innovative therapeutic candidate for the treatment of restenosis.

Mathematical modeling in assessing the risk of restenosis after carotid endarterectomy.

Carotid endarterectomy is the main way to combat atherosclerosis of the carotid arteries, which disrupts cerebral circulation. The generally accepted marker of atherogenesis risk are hemodynamic indices associated with near-wall shear stress. The purpose of the work is to conduct a comparative analysis of hemodynamic indices in various carotid bifurcation models. The influence of a virtual change in the geometric shape of the model in order to optimize hemodynamic indices is also being studied. On the basis of computed angiography data, carotid bifurcation models are constructed, in which critical zones of hemodynamic indices are built using computational fluid dynamics. A comparative analysis of the critical zones for different classes of models is carried out. Comparison of averaged indices for critical zones between 'normal' and post-operative groups gave more than 5-x worse results for the latter. The same results for the near-bifurcation parts of the zones give a 25% better result for postoperative models. Virtual 'removal' of insignificant plaques leads to a deterioration of the indices of up to 40% in the places of the plaque's former location. The described method makes it possible to build the indices critical zones and compare them for various types of models. A technique for virtual changing the shape of a vessel (virtual surgery) is proposed. The novelty of the approach lies in the use for comparative analysis both real vessel models and hypothetical 'improved' virtual ones, as well in the proposed division of post-operative model's critical zones into subzones of different genesis.

Triple platelet inhibition in intracranial thrombectomy with additional acute cervical stent angioplasty due to tandem lesion: a retrospective single-center analysis.

BACKGROUND: Acute stroke treatment with intracranial thrombectomy and treatment of ipsilateral carotid artery stenosis/occlusion ("tandem lesion", TL) in one session is considered safe. However, the risk of stent restenosis after TL treatment is high, and antiplatelet therapy (APT) preventing restenosis must be well balanced to avoid intracranial hemorrhage. We investigated the safety and 90-day outcome of patients receiving TL treatment under triple-APT, focused on stent-patency and possible disadvantageous comorbidities. METHODS: Patients receiving TL treatment in the setting of acute stroke between 2013 and 2022 were analyzed regarding peri-/postprocedural safety and stent patency after 90 days. All patients received intravenous eptifibatide and acetylsalicylic acid and one of the three drugs prasugrel, clopidogrel, or ticagrelor. Duplex imaging was performed 24 h after treatment, at discharge and 90 days, and digital subtraction angiography was performed if restenosis was suspected. RESULTS: 176 patients were included. Periprocedural complications occurred in 2.3% of the patients at no periprocedural death, and in-hospital death in 13.6%. Discharge mRS score was maintained or improved at the 90-day follow-up in 86%, 4.54% had an in-stent restenosis requiring treatment at 90 days. No recorded comorbidity considered disadvantageous for stent patency showed statistical significance, the duration of the endovascular procedure had no significant effect on outcome. CONCLUSION: In our data, TL treatment with triple APT resulted in a low restenosis rate, low rates of sICH and a comparably high number of patients with favorable outcome. Aggressive APT in the initial phase may therefore have the potential to prevent recurrent stroke better than restrained platelet inhibition. Comorbidities did not influence stent patency.

Endovascular mechanical thrombectomy of iliofemoral venous stent occlusion with the novel RevCore thrombectomy system: case reports and literature review.

Venous in-stent restenosis is not completely understood, and the currently available treatment is usually unsatisfactory. We describe the cases of two patients treated with the RevCore thrombectomy system (Inari Medical), designed for venous in-stent thrombosis. Case 1 involves a 62-year-old woman with post-thrombotic syndrome from iliac vein stent placement 15 years earlier. Case 2 describes a 30-year-old woman with post-thrombotic syndrome from recurrent iliac vein stent occlusion, despite therapeutic anticoagulation. Both patients had previous recanalization attempts at outside facilities that were unsuccessful. The RevCore system was safe and feasible in these initial cases, and more studies are warranted.