Prevention Of Restenosis Research Articles

Metabolomics revealed pharmacodynamic effects of aspirin and indobufen in patients after percutaneous transluminal angioplasty surgery.

Aspirin and indobufen are commonly used therapeutic drugs for the prevention of vascular restenosis (VR) after percutaneous transluminal angioplasty surgery. They both exhibited antiplatelet effects but molecular mechanisms underlying metabolic changes induced by them remain unclear. In this study, we collected plasma samples from patients on aspirin medication (n = 5), patients on indobufen medication, patients with no medication after PTA, and healthy controls (CKs) (n = 5). Our investigation aimed to reveal the metabolic processes in patients during vascular restenosis and its amelioration through drug therapy using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our data showed significant alterations in amino acid and choline metabolism in patients without medication after PTA. Aspirin and indobufen were able to regulate these metabolic pathways to alleviate VR symptoms. We identified several characteristic amino acids, including pro-leu, L-citrulline, his-glu, and L-glutamate, as important biomarkers for VR assessment in patients without medication after PTA. A total of 17 and 4 metabolites involved in arginine and phenylalanine metabolism were specifically induced by aspirin and indobufen, respectively. Their expression levels were significantly regulated by aspirin or indobufen, nearly reaching normal levels. Taken together, our identification of metabolites involved in metabolic changes affected by aspirin and indobufen medication enhances the understanding of VR pathology after PTA. This may help identify early diagnostic biomarkers and therapeutic targets.

Prevention and Management of Restenosis After Coronary Interventional Therapy

Percutaneous coronary intervention (PCI) is one of the key methods for treating coronary heart disease, yet post-procedural restenosis remains a significant clinical challenge. Restenosis refers to the re-narrowing of the coronary artery after PCI due to factors such as neointimal hyperplasia and smooth muscle cell proliferation, which adversely affects blood flow restoration and patient prognosis. To address this issue, this study systematically explores strategies for the prevention and management of restenosis. Effective preventive measures are discussed in terms of pharmacological prevention, stent selection, optimization of procedural techniques, and lifestyle interventions. Additionally, the article analyzes pharmacological treatment options and re-intervention strategies for patients experiencing restenosis. The findings indicate that personalized treatment plans, optimized stent selection, rigorous postoperative management, and long-term monitoring are key to reducing the incidence of restenosis. Future research should further investigate the application of genetic testing and smart healthcare technologies in the management of restenosis.

Provinols™, a Polyphenolic Extract of Red Wine, Inhibits In-Stent Neointimal Growth in Cholesterol-Fed Rabbit.

Background/Objectives: Epidemiological studies indicate a potential correlation between the consumption of polyphenols and a reduced risk of developing cardiovascular disorders. The present study investigates the potential of a red wine polyphenol oral extract, Provinols™, to reduce neointimal hyperplasia following angioplasty in a hypercholesterolemic rabbit model. Methods: New Zealand white rabbits were fed 1% cholesterol-enriched chow for a period of eight weeks prior to the induction of iliac balloon injury and subsequent stent placement. Following the implantation of the stent, Provinols™ (20 mg/kg/day) or an identical placebo was administered orally for a period of four weeks in a randomized manner. Twenty-eight days following the stenting procedure, the arteries were harvested after euthanasia and subjected to histology assignment analysis. Results: The administration of Provinols™ did not result in a statistically significant change in either blood pressure or plasma cholesterol levels. However, Provinols™ treatment led to a notable reduction in the growth of the intima within the stented area, as well as a reduction in the thickness and surface area of the intima. It is of note that treatment with Provinols™ was associated with a reduction in the accumulation of fat within the arteries and a diminished inflammatory response to injury. Conclusions: The findings demonstrate that oral administration of Provinols™ has the potential to reduce in-stent neointimal growth and lipid deposition, likely due to its anti-inflammatory properties in iliac arteries from hypercholesterolemic rabbits. Additionally, these findings provide an evidence-based rationale for the potential therapeutic benefits of plant-derived polyphenols in the prevention of restenosis associated with stent placement.

In vivo biocompatibility of a new hydrophobic coated Al/Al2O3 nanowire surface on stents

BackgroundIntima proliferation and in-stent restenosis is a challenging situation in interventional treatment of small vessel obstruction. Al/Al2O3 nanowires have been shown to accelerate vascular endothelial cell proliferation and migration in vitro, while suppressing vascular smooth muscle cell growth. Moreover, surface modification of Al/Al2O3 nanowires with poly[bis(2,2,2-trifluoromethoxy)phosphazene (PTFEP) coating enables further advantages such as reduced platelet adhesion. Therefore, the study's goal was to compare the biocompatibility of novel Al/Al2O3 + PTFEP coated nanowire bare-metal stents to uncoated control stents in vivo using optical coherence tomography (OCT), quantitative angiography and histomorphometric assessment. Methods15 Al/Al2O3 + PTFEP coated and 19 control stents were implanted in the cervical arteries of 9 Aachen minipigs. After 90 days, in-stent stenosis, thrombogenicity, and inflammatory response were assessed. Scanning electron microscopy was used to analyse the stent surface. ResultsOCT analysis revealed that neointimal proliferation in Al/Al2O3 + PTFEP coated stents was significantly reduced compared to control stents. The neointimal area was 1.16 ± 0.77 mm2 in Al/Al2O3 + PTFEP coated stents vs. 1.98 ± 1.04 mm2 in control stents (p = 0.004), and the neointimal thickness was 0.28 ± 0.20 vs. 0.47 ± 0.10 (p = 0.003). Quantitative angiography showed a tendency to less neointimal growth in coated stents. Histomorphometry showed no significant difference between the two groups and revealed an apparent inflammatory reaction surrounding the stent struts. ConclusionsAt long-term follow-up, Al/Al2O3 + PTFEP coated stents placed in peripheral arteries demonstrated good tolerance with no treatment-associated vascular obstruction and reduced in-stent restenosis in OCT. These preliminary in vivo findings indicate that Al/Al2O3 + PTFEP coated nanowire stents may have translational potential to be used for the prevention of in-stent restenosis.

Application of Photodynamic Therapy in Cardiology.

The origins of photodynamic therapy (PDT) date back to 1904. Since then, the amount of research proving PDT and, consequently, its applicability to various disease states has steadily increased. Currently, PDT is mainly used in oncology to destroy cancer cells. It is being worked on for possible use in other medical fields as well, including cardiology. It can be used in the prevention of restenosis, often occurring after vascular surgical interventions, for destroying atherosclerotic plaques and as a new ablative method of ectopic centers in the treatment of atrial fibrillation. The purpose of this review is to summarize the knowledge to date regarding the therapeutic potential of using PDT for various pathological conditions in cardiology. The review also focuses on the current limitations associated with the use of PDT and identifies areas where more research is needed to develop better drug regimens. Materials and methods: The study analyzed 189 medical articles. The articles came from PubMed, Frontiers, Google Scholar, Science Direct and Web of Science databases. Through the excitation of light, a photosensitizer (PS) introduced into the body, the destruction of pathological cells occurs. PTD is widely used in oncology of the central nervous system (CNS). This process is made possible by the production of free oxygen radicals (ROS) and singlet oxygen, which generate oxidative stress that destroys sensitive cancer cells. In recent years, photosensitizers have also been discovered to have a strong affinity for macrophages that fill atherosclerotic plaques, making these compounds suitable for treating atherosclerosis. By inducing apoptosis of smooth muscle cells, inactivating basic fibroblast growth factor (FGF-β) and inhibiting endothelial cell hyperplasia, PDT can be used to prevent restenosis after surgical proceduresPDT appears to be a minimally invasive and highly effective therapeutic method, especially when combined with other therapeutic methods. Unfortunately, the small number of animal model studies and human clinical trials greatly limit the applicability of PDT on a wider scale. Current limitations, such as the depth of penetration, delivery of photosensitizer particles to the direct site of the lesion or the appropriate choice of photosensitizer in relation to the nature of the pathology, unfortunately make it impossible to replace current therapeutic approaches.

Cilostazol for peripheral arterial disease - a position paper from the Italian Society for Angiology and Vascular Medicine.

Cilostazol is a quinolinone-derivative selective phosphodiesterase inhibitor and is a platelet-aggregation inhibitor and arterial vasodilator for the symptomatic treatment of intermittent claudication (IC). Cilostazol has been shown to improve walking distance for patients with moderate to severe disabling intermittent claudication who do not respond to exercise therapy and who are not candidates for vascular surgical or endovascular procedures. Several studies evaluated the pharmacological effects of cilostazol for restenosis prevention and indicated a possible effect on re-endothelialization mediated by hepatocyte growth factor and endothelial precursor cells, as well as inhibiting smooth muscle cell proliferation and leukocyte adhesion to endothelium, thereby exerting an anti-inflammatory effect. These effects may suggest a potential effectiveness of cilostazol in preventing restenosis and promoting the long-term outcome of revascularization interventions. This review aimed to point out the role of cilostazol in treating patients with peripheral arterial disease, particularly with IC, and to explore its possible role in restenosis after lower limb revascularization.

Comparing Endovascular Approaches in Lower Extremity Artery Disease: Insights from a Network Meta-Analysis.

Endovascular therapy offers an alternative for treating femoropopliteal (FP) and infrapopliteal (IP) lesions related to occlusive lower extremity artery disease. Despite numerous trials, the effectiveness of restenosis prevention using local drug delivery devices remains a topic of debate. An updated systematic review and network meta-analysis was conducted. Our overall aim was to summarize the most recent clinical evidence regarding endovascular approaches for FP and IP atherosclerotic lesions. We conducted a search for randomized trials in the MEDLINE database, and extracted data related to clinical endpoints. Our primary focus was on the rate of major adverse events (MAEs), including mortality, amputation, and target lesion revascularization (TLR). A multiple treatment network meta-analysis supplemented with component network analyses was performed to examine the impact of combined treatment. Our search yielded 33 randomized controlled trials encompassing 5766 patients. This included 19 studies focused on femoropopliteal and 14 on IP lesions, accounting for 3565 and 2201 patients, respectively. Drug-coated balloons (DCBs) and drug-eluting stents (DESs) displayed a reduced MAE risk in comparison to plain old balloon angioplasty (POBA)-RR for DCB: 0.64 (95% CI: 0.52-0.77) and for DES: 0.71 (95% CI: 0.51-0.99). The bare-metal stent (BMS) group manifested the most substantial MAE risk, being 59% higher relative to the DCB cohort (BMS vs. DCB RR: 1.59; 95% CI: 1.03-2.47). For FP lesions, DES was the standout performer, curtailing MAE risk by 55% relative to POBA. Within IP lesions, DES mitigated the MAE risk by 25% versus POBA. DCB did not exhibit any notable MAE reduction when pitted against POBA. In FP arteries, both DESs and DCBs yielded significantly diminished MAEs, thus outpacing other techniques. Regarding IP arteries, only DESs resulted in significantly fewer MAEs. In alignment with contemporary research, our findings revealed no signs of elevated mortality in patients undergoing treatment with drug-eluting apparatuses.

SGLT2 inhibitor improves the prognosis of patients with coronary heart disease and prevents in-stent restenosis.

Coronary heart disease is a narrowing or obstruction of the vascular cavity caused by atherosclerosis of the coronary arteries, which leads to myocardial ischemia and hypoxia. At present, percutaneous coronary intervention (PCI) is an effective treatment for coronary atherosclerotic heart disease. Restenosis is the main limiting factor of the long-term success of PCI, and it is also a difficult problem in the field of intervention. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral glucose-lowering agent used in the treatment of diabetes in recent years. Recent studies have shown that SGLT2 inhibitors can effectively improve the prognosis of patients after PCI and reduce the occurrence of restenosis. This review provides an overview of the clinical studies and mechanisms of SGLT2 inhibitors in the prevention of restenosis, providing a new option for improving the clinical prognosis of patients after PCI.

Meta-analysis of risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease.

The aim of this study was to investigate the risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease (ICVD), and to provide a reference for potential measures to prevent ICVD. Relevant studies were identified by searching PubMed, ScienceDirect and Web of Science databases. Combined adjusted odds ratios and 95% confidence intervals were calculated. Seven case-control studies were identified in the end. Diabetes mellitus and residual stenosis were the two main risk factors for restenosis (OR = 0.59, 95% CI: 0.39-0.91, p = 0.01; OR = 36.73, 95% CI: 19.72-70.02, p < 0.001). Gender, smoking, hypertension, dyslipidemia, and stent type were not significantly associated with restenosis (OR = 0.85, 95% CI: 0.53-1.38, p = 0.52; OR = 1.30, 95% CI: 0.91-1.86, p = 0.15; OR = 0.86, 95% CI: 0.16-4.66, p = 0.86; OR = 1.30, 95% CI: 0.58-2.91, p = 0.53; OR = 1.34, 95% CI: 0.72-2.48, p = 0.35). The prevention of restenosis after stenting is particularly important for ICVD patients with diabetes or a high residual stenosis rate.

Efficiency and safety of dual pathway inhibition for the prevention of femoropopliteal artery restenosis in repeated endovascular interventions

ObjectiveThere is a lack of consensus regarding the optimal strategy for evaluating the efficiency and safety of dual-pathway inhibition (DPI) in preventing femoropopliteal restenosis in patients undergoing repeated endovascular interventions. Despite several therapeutic interventions available for preventing femoropopliteal restenosis post repeated endovascular interventions, the ideal strategy, particularly evaluating the efficacy and safety of DPI, remains a matter of debate. MethodsFrom January 2015 to September 2021, patients who underwent repeated endovascular interventions for femoropopliteal restenosis were compared with those who underwent DPI or dual antiplatelet therapy (DAPT) after surgery using a propensity score-matched analysis. The primary outcome was clinically driven target lesion revascularization (CD-TLR). The principal safety outcome was a composite of major bleeding and clinically relevant non-major (CRNM) bleeding. To further enhance the rigor, Kaplan-Meier plots, Cox proportional hazards modeling, and sensitivity analyses, as well as subgroup analyses were employed, reducing potential confounders. ResultsA total of 441 patients were included in our study, of whom 294 (66.7%) received DAPT and 147 (33.1%) received DPI, with 114 matched pairs (mean age, 72.21 years; 84.2% male). Cumulative probability of CD-TLR at 36 months in the DPI group (17%) trended lower than that in the DAPT group (32%) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.78; P =.004). The cumulative probability of freedom from CD-TLR at 36 months in the DPI group was 83%. No significant difference was observed in the composite outcome of major or CRNM bleeding between the DPI and DAPT groups (HR, 1.26; 95% CI, 0.34 to 4.69; P = .730). The DPI group was associated with significantly lower rates of CD-TLR in the main subgroup analyses of diabetes (P = .001), previous smoking history (P = .008), longer lesion length (>10 cm) (P = .003), and treatment with debulking strategy (P = .003). ConclusionsIn our investigation focused on CD-TLR, we found that DPI exhibited a significant reduction in the risk of reintervention compared with other treatment modalities. This underscores the potential of DPI as a viable therapeutic strategy in preventing reinterventions. Moreover, our assessment of safety outcomes revealed that the bleeding risks associated with DPI were on par with DAPT, thereby not compromising patient safety. These findings pave the way for potential broader clinical implications, emphasizing the effectiveness and safety of DPI in the context of reducing reintervention risks.

Ultrasound-mediated delivery of Pik3cb shRNA using magnetic nanoparticles for the treatment of in-stent restenosis in a rat balloon-injured model.

The aim of the present work was to examine the effect of polyethylene glycol (PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles carrying Pik3cb short hairpin RNA (shRNA) in the prevention of restenosis with the aid of ultrasound and a magnetic field. SPIO is a type of contrast agent used in medical imaging to enhance the visibility of specific tissues or organs. It consists of tiny iron oxide nanoparticles that can be targeted to specific areas of interest in the body. PEG-coated SPIO nanoparticles carrying Pik3cb shRNA (SPIO-shPik3cb) were prepared, and the particle size and zeta potential of PEG-coated SPIO nanoparticles with and without Pik3cb shRNA were examined. After a right common artery balloon-injured rat model was established, the rats were randomly divided into four groups, and the injured arteries were transfected with SPIO-shPik3cb, saline, SPIO-shcontrol and naked shRNA Pik3cb. During the treatment, each group was placed under a magnetic field and was transfected with the aid of ultrasound. Rats were sacrificed, and the tissue was harvested for analysis after 14days. The results suggested that the mean particle size and zeta potential of SPIO-shPik3cbs were 151.45 ± 11nm and 10mV, respectively. SPIO-shPik3cb showed higher transfection efficiency and significantly inhibited the intimal thickening compared with naked Pik3cb shRNA in vascular smooth muscle cells (VSMCs) (*P < 0.05). Moreover, SPIO-shPik3cb could also significantly downregulate the expression of pAkt protein compared with naked Pik3cb shRNA. According to the results, SPIO-shPik3cb can remarkably inhibit the intimal thickening under a combination of magnetic field exposure and ultrasound.

Abstract 11635: Device and Formulation Optimization for MK2 Inhibition and Restenosis Prevention at Sites of Peripheral Angioplasty

Introduction: Peripheral angioplasty often fails due to intimal hyperplasia (IH), where contractile smooth muscle cells (SMCs) de-differentiate into proliferative, migratory, and pro-inflammatory synthetic SMCs, leading to restenosis. We have formerly shown that potentiation of an MK2 inhibitory peptide (MK2i) via delivery with poly(propyl acrylic acid) (PPAA) can block SMC phenotype switching and neointima formation in a transplant model. This work develops strategies for targeted in vivo MK2i+PPAA delivery to the site of angioplasty. Hypothesis: MK2i+PPAA can be effectively delivered into and retained within the arterial wall using either convective delivery or a coated angioplasty balloon. Methods: These studies have utilized isolated rat aortae as a model tissue. Aortae were balloon damaged and subjected to convective or coated balloon treatment. Delivery and retention of MK2i was determined with confocal microscopy and flow cytometry. MK2i activity was measured using IHC and western blots for pCREB, a downstream substrate of MK2. Results: Convective delivery studies have shown substantial MK2i delivery into the vascular wall, with pre-formed MK2i nanopolyplexes (NPs) having significantly more cell uptake than free MK2i or sequentially delivered PPAA and MK2i. Additionally, we have created a method for layered coating of MK2i+PPAA onto an angioplasty balloon that shows rapid release and successful arterial wall delivery. In efficacy studies, convective delivery of MK2i-NPs and balloon delivery of MK2i+PPAA with 50 mg/mL lactosucrose excipient significantly decreased levels of pCREB downstream of MK2 after balloon damage. Ongoing studies show that both delivery strategies block cellular proliferation in balloon damaged arteries after 7d in a flow loop bioreactor. Conclusions: Convective and coated balloon delivery show promise as strategies for on-target delivery of MK2i+PPAA to peripheral arteries after angioplasty to prevent restenosis.

Decoding the Polyphenol Impact on the Cardiovascular System: A Journey from the French Paradox to Restenosis

&#x0D; Resveratrol and quercetin, two natural polyphenolic compounds, exhibit potential in veterinary and human medicine for cardiovascular benefits, particularly for the prevention and management of restenosis, a complex process involving blood vessel re-narrowing. This review investigates the impact of these compounds on restenosis in animal models, explaining their modes of action, which include antioxidant, anti-inflammatory, and anti-proliferative capabilities. Additional insights are provided by the intriguing "French Paradox," in which the Southern French population's low heart disease incidence is associated with red wine and polyphenol-rich diet consumption. Through animal models, we gain essential knowledge about the therapeutic potential, safety, and dosing of resveratrol and quercetin in both veterinary and human clinical settings. Understanding their precise molecular pathways is essential in enhancing their effectiveness in reducing restenosis. The "French Paradox" draws attention to the potential cardiovascular benefits of polyphenols in restenosis. Novel approaches to minimize restenosis in veterinary and human medicine may result from bridging the gap between animal models and human trials.&#x0D;

Drug-coated balloon for treatment of non-atherosclerotic renal artery stenosis—a multi-center study

IntroductionRenal artery stenosis (RAS) is a significant reason for secondary hypertension. Impaired renal function and subsequent cardiopulmonary dysfunction could also occur. Patients of non-atherosclerotic RAS has a relatively young age and long life expectancy. Revascularization with percutaneous transluminal angioplasty (PTA) is a viable treatment option. However, restenosis is unavoidable which limits its use. Drug-coated balloon (DCB) has been proven to be effective in restenosis prevention in femoropopliteal arterial diseases and in patients with renal artery stenosis. And PTA for Renal artery fibromuscular dysplasia is safe and clinically successful. Therefore, we could speculate that DCB might have potential efficacy in non-atherosclerotic RAS treatment.Methods and analysisThis will be a randomized multi-center-controlled trial. Eighty-four eligible participants will be assigned randomly in a 1:1 ratio to the control group (plain old balloon, POB) and the experimental group (DCB). Subjects in the former group will receive balloon dilatation alone, and in the latter group will undergo the DCB angioplasty. The DCB used in this study will be a paclitaxel-coated balloon (Orchid, Acotec Scientific Holdings Limited, Beijing, China). Follow-up visits will be scheduled 1, 3, 6, 9, and 12 months after the intervention. Primary outcomes will include controlled blood pressure and primary patency in the 9-month follow-up. Secondary outcomes will include technical success rate, complication rate, and bail-out stenting rate.Trial registrationClinicalTrials.gov (number NCT 05858190).Protocol version V.4 (3 May 2023).

Preoperative sizing and prevention of in-stent restenosis in patients with peripheral arterial occlusive disease

Preoperative sizing and prevention of in-stent restenosis in patients with peripheral arterial occlusive disease

Gas station in blood vessels: An endothelium mimicking, self-sustainable nitric oxide fueling stent coating for prevention of thrombosis and restenosis

Stenting is the primary treatment for vascular obstruction-related cardiovascular diseases, but it inevitably causes endothelial injury which may lead to severe thrombosis and restenosis. Maintaining nitric oxide (NO, a vasoactive mediator) production and grafting endothelial glycocalyx such as heparin (Hep) onto the surface of cardiovascular stents could effectively reconstruct the damaged endothelium. However, insufficient endogenous NO donors may impede NO catalytic generation and fail to sustain cardiovascular homeostasis. Here, a dopamine-copper (DA-Cu) network-based coating armed with NO precursor L-arginine (Arg) and Hep (DA-Cu-Arg-Hep) is prepared using an organic solvent-free dipping technique to form a nanometer-thin coating onto the cardiovascular stents. The DA-Cu network adheres tightly to the surface of stents and confers excellent NO catalytic activity in the presence of endogenous NO donors. The immobilized Arg functions as a NO fuel to generate NO via endothelial nitric oxide synthase (eNOS), while Hep works as eNOS booster to increase the level of eNOS to decompose Arg into NO, ensuring a sufficient supply of NO even when endogenous donors are insufficient. The synergistic interaction between Cu and Arg is analogous to a gas station to fuel NO production to compensate for the insufficient endogenous NO donor in vivo. Consequently, it promotes the reconstruction of natural endothelium, inhibits smooth muscle cell (SMC) migration, and suppresses cascading platelet adhesion, preventing stent thrombosis and restenosis. We anticipate that our DA-Cu-Arg-Hep coating will improve the quality of life of cardiovascular patients through improved surgical follow-up, increased safety, and decreased medication, as well as revitalize the stenting industry through durable designs.

Mechanistic exploration of Yiqi Liangxue Shengji prescription on restenosis after balloon injury by integrating metabolomics with network pharmacology

Context Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI). Objective To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology. Materials and methods Forty male Sprague–Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC–MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated. Results Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p < 0.01) and reduced intima thickness by H&E (30.12 ± 6.05 μm vs. 14.32 ± 1.37 μm, p < 0.01). We identified 18 differential metabolites and 5 core targets such as inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor-A (VEGFA), ornithine decarboxylase-1 (ODC1) and group IIA secretory phospholipase A2 (PLA2G2A). These targets were further confirmed by molecular docking and ELISA. Discussion and conclusions This study confirms the effects of YQLXSJ on restenosis and reveals some biomarkers. TCM has great potential in the prevention and treatment of restenosis by improving metabolic disorders.

Allicin-Loaded Intelligent Hydrogel Coating Improving Vascular Implant Performance.

Coronary atherosclerosis is closely related to inflammation and oxidative stress. Owing to poor biocompatibility, lack of personalized treatment, and late toxic side effects, traditional drug-eluting stent intervention, releasing antiproliferative drugs, can delay endothelial repair and cause late thrombosis. The inflammation caused by atherosclerosis results in an acidic microenvironment and oxidative stress, which can be considered as triggers for precise and intelligent treatment. Here, we used catechol hyaluronic acid (C-HA) and cystamine (Cys) to prepare C-HA-Cys hydrogel coatings by amide reaction. The H2S-releasing donor allicin was loaded in the hydrogel to form an intelligent biomimetic coating. The disulfide bond of Cys made the cross-linked network redox-responsive to the inflammation and oxidative stress in the microenvironment by releasing the drug and H2S intelligently to combat the side effects of stent implantation. This study evaluated the hemocompatibility, anti-inflammatory capacity, vascular wall cytocompatibility, and in vivo histocompatibility of this intelligent hydrogel coating. Furthermore, the effect of H2S released from the coating on atherosclerosis-related signaling pathways such as CD31 and cystathionine γ-lyase (CSE), CD36, and ACAT-1 was investigated. Our results indicate that the C-HA-Cys-Allicin hydrogel coating could be manufactured on the surface of vascular interventional devices to achieve a precise response to the microenvironment of the lesion to release drug, which can attain the purpose of prevention of in-stent restenosis and ensure the effectiveness and safety of the application of interventional devices.

Sirolimus-loaded exosomes as a promising vascular delivery system for the prevention of post-angioplasty restenosis.

Restenosis remains the main reason for treatment failure of arterial disease. Sirolimus (SIR) as a potent anti-proliferative agent is believed to prevent the phenomenon. The application of exosomes provides an extended-release delivery platform for SIR intramural administration. Herein, SIR was loaded into fibroblast-derived exosomes isolated by ultracentrifugation. Different parameters affecting drug loading were optimized, and exosome samples were characterized regarding physicochemical, pharmaceutical, and biological properties. Cytotoxicity, scratch wound assays, and quantitative real-time PCR for inflammation- and migration-associated genes were performed. Restenosis was induced by carotid injury in a rat carotid model and then exosomes were locally administered. After 14days, animals were investigated by computed tomography (CT) angiography, morphometric, and immunohistochemical analyses. Western blotting confirmed the presence of specific protein markers in exosomes. Characterization of empty and SIR-loaded exosomes verified round and nanoscale structure of vesicles. Among prepared formulations, desired entrapment efficiency (EE) of 76% was achieved by protein:drug proportion of 2:1 and simple incubation for 30min at 37°C. Also, the optimal formulation released about 30% of the drug content during the first 24h, followed by a prolonged release for several days. In vitro studies revealed the uptake and functional efficacy of the optimized formulation. In vivo studies revealed that %restenosis was in the following order: saline > empty exosomes > SIR-loaded exosomes. Furthermore, Ki67, alphasmooth muscle actin (α-SMA), and matrix metalloproteinase (MMP) markers were less expressed in the SIR-exosomes-treated arteries. These findings confirmed that exosomal SIR could be a hopeful strategy for the prevention of restenosis.

THE RISKS AND BENEFITS OF RENAL ARTERY STENTING IN FIBROMUSCULAR DYSPLASIA. LESSONS FROM ARCADIA-POL STUDY

Objective: Percutaneous transluminal angioplasty (PTA) is the recommended revascularization strategy in patients with renal artery stenosis (RAS) caused by fibromuscular dysplasia (FMD), limiting stenting to complications management. However this recommendation is based on cases reports and small series. The main aim of the study was to retrospectively analyze immediate and long-term results of renal stenting and PTA in FMD patients. The second aim was to evaluate the results of stenting as support of renal artery aneurysm (RAA) closure. Design and method: The study group consisted of 58 patients percutaneously treated due to significant RAS (70 arteries) and 9 patients (10 RAAs) with a history of stent implantation before aneurysm embolization, derived from 343 ARCADIA-POL registry patients. PTA was performed as initial treatment in 61 arteries (PTA-group), whereas primary stenting was done in 9 arteries (STENT-group). Stent-related complications(SRC) were defined as: in-stent restenosis (&gt;50%) or occlusion (ISR/O); stent fracture; stent underexpansion (SU) or migration. Results: In PTA-group, the first restenosis rate was 50.8%. Subsequently, 22 arteries underwent a second procedure: re-PTA(12 arteries) or stent implantation(10 arteries) . The incidence of recurrent restenosis after re-PTA was 41.7%. In the 10 arteries initially treated with PTA that underwent stenting for restenosis, complications occurred in 7 of them (70%), including 2 SUs and 5 ISR/Os . In STENT-group, SU occurred in one case (11.1%) and in-stent restenosis in 33.3% (3 of 9 stents). In combined analysis, SRC occurred following 11/19 stenting procedures (57.9%) including 3 periprocedural (SUs) and 8 late complications (ISR/Os). Finally, despite several subsequent revascularization attempts, 4 of 19 (21%) stented arteries were totally occluded and one remained significantly stenosed at follow-up imaging (Figure). In contrast to FMD-RAS procedures, there was only one intraprocedural complication (partial stent migration) and no late SRC in RAA patients. Conclusions: Renal artery stenting in FMD provides modest benefit in terms of restenosis prevention but poses high risk of immediate and late complications, including stent occlusion. Our study supports recommendations limiting stenting to the management of complications. In contrast, renal artery stenting in FMD RAA closure is associated with favorable long-term outcomes.