Prevention Of Restenosis Research Articles

UV-modified and dual-catalytic Cu porphyrin-loaded TiO2 nanotubes with enhanced hemocompatibility and prevention of stent restenosis

Implanting vascular stents is regarded as a ground-breaking technique for treating cardiovascular disorders. Thus, advancements in vascular stent technology and stent materials have significant social and economic implications. The development of a surface with bionic endothelial function of nitric oxide (NO) release is always an ideal direction for cardiovascular material modification. However, The NO-release stents will face severe challenges in the oxidative stress microenvironment of atherosclerotic lesions. Excessive reactive oxygen species (ROS) can delay scaffold surface re-endothelialization by causing rapidly oxidative inactivation of NO and by causing endothelial cells (ECs) to undergo apoptosis. Regulating the oxidative stress microenvironment is crucial to address the aforementioned issues. In this study, a composite material that contains ultraviolet (UV)-modified and Copper (II) meso-tetra(4-carboxyphenyl) porphine (CuTPP)-loaded titanium dioxide nanotubes (NTs) was presented. CuTPP can efficiently catalyze the decomposition of ROS and also decompose GSNO into NO. As a unique technique, UV irradiation was used to enhance the anticoagulant properties of the CuTPP-loaded NTs (NTs@Cu). In vivo and in vitro results demonstrated that UV treated NTs@Cu maintained strong biocompatibility, anti-thrombosis, ECs and smooth muscle cells (SMCs) regulation, and anti-inflammatory capabilities. This technique might present a fresh idea for developing brand-new NO-release scaffolds.

Sulfasalazine induces autophagy inhibiting neointimal hyperplasia following carotid artery injuries in mice.

Background: Neointimal hyperplasia (NH) is a crucial pathophysiological feature in vascular transplant and in-stent restenosis. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in neointimal hyperplasia. This study aims to explore the potentialities and mechanism of sulfasalazine (SSZ) in the prevention of restenosis. Methods: Sulfasalazine was encapsulated in nanoparticles made of poly (lactic-co-glycolic acid) (PLGA). In vivo, carotid ligation injury was induced in mice to induce Neointimal hyperplasia, with or without sulfasalazine containing nanoparticles (NP-SSZ) treatment. After 4weeks, the arteries were collected for histology, immunofluorescence, Western blotting (WB) and qRT-PCR. In vitro, vascular smooth muscle cells were treated with TNF-α to induce cell proliferation and migration, followed by SSZ or vehicle treatment. WB was performed to further explore its mechanism. Results: The ratio of intima to media thickness (I/M) was increased after ligation injury on day 28, while the ratio was significantly reduced in the NP-SSZ treatment group. The dual positive nuclei of Ki-67 and α-SMA were 47.83% ± 9.15%, whereas only 29.83% ± 5.98% in the NP-SSZ-treated group (p < 0.05). Both MMP-2 and MMP-9 were decreased in the NP-SSZ treatment group (p < 0.05, p < 0.05, respectively) compared to the control group. The levels of the targeted inflammatory genes (TNF-α, VCAM-1, ICAM-1, MCP-1) were lower in the NP-SSZ treatment group compared with the control group. In vitro, the proliferating cell nuclear antigen (PCNA) expression was significantly decreased in the SSZ treatment group. The cell viability of VSMCs was markedly increased in the TNF-α treatment group, whereas sulfasalazine treatment inhibited this effect. LC3 II and P62 protein expression were higher in the SSZ group than in the vehicle group both in vitro and in vivo. The phosphorylation of NF-kB (p-NF-kB) and the phosphorylation of mTOR (p-mTOR) were decreased in the TNF-α+ SSZ group, whereas the P62 and LC3 II expression levels were increased. However, the expression level of p-mTOR, P62, and LC3 II was reversed after co-treatment with the agonist of mTOR MHY1485, whereas the p-NF-kB expression level was unchanged. Conclusion: sulfasalazine inhibited vascular smooth muscle cells proliferation and migration in vitro and Neointimal hyperplasia in vivo through NF-kB/mTOR-mediated autophagy.

Efficacy Assessment and Mechanism Exploration of Multiple Functional Peptide on Restenosis Prevention

Restenosis is a common complication after balloon angioplasty, and the major mechanism is associated with abnormal proliferation and migration of vascular smooth muscle cells. To date, most of the clinically used vascular stent drugs are possessed of non-selective cytotoxic effects, which seriously affect the re-endothelialization of vascular endothelial cells, and increase the chances to form thrombosis and neointimal hyperplasia.Different haptoglobin (Hp) phenotypes have been clinically confirmed to be related to the incidence of restenosis. In our preliminary studies, Hp subunits also showed a variety of potential activities to inhibit restenosis. Therefore, the aim of this study is to explore if multiple functional peptide (MFP) of Hp subunits can be the potential protein drugs for preventing restenosis.The efficacy of MFP on resteneosis was evaluated by in vivo and in vitro studies. In the i n vivo study, male Sprague Dawley (SD) rats were subjected to tail vein injection of MFP twice a week right after the balloon angioplasty on common carotid artery. Two weeks after the angioplasty, the injured arteries were harvested for pathological assessment on neointimal formation by H&amp;E staining.In the in vitro stduy, both endothelial cells (HUVEC) and smooth muscle cells (A10) were treated with various concentrations of MFP to evaluate their effects on cellular proliferation and migration. The antioxidant effects of MFP on malondialdehyde (MDA) formation and superoxide dismutase (SOD) activities were also assayed on macrophage cells.Our results demonstrated that in vivo administration of MFP can significantly suppress the neointimal formation induced by angioplasty. The positive regulatory effects of MFP on cellular proliferaiton and migration of HUVEC and negative effects on A10 may be the key molecular mechainsms of MFP on suppressing the neointimal formation found in the in vivo study. The antioxidant effects of MFP may also contribute to diminish the neointimal formation. The outcomes of this study will help to understand the feasibility, efficacy and safety of MFP as potential protein drug candidates for preventing vascular restenosis. National Science and Technology Council This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis

BackgroundWe performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy.MethodsEpithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations.ResultsSubject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth.ConclusionsSubjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis.Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

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

Vein grafts are widely used for coronary artery bypass grafting and hemodialysis access, but restenosis remains the "Achilles' heel" of these treatments. An extravascular stent is one wrapped around the vein graft and provides mechanical strength; it can buffer high arterial pressure and secondary vascular dilation of the vein to prevent restenosis. In this study, we developed a novel Nanocellulose-gelatin hydrogel, loaded with the drug Astragaloside IV (AS-IV) as an extravascular scaffold to investigate its ability to reduce restenosis. We found that the excellent physical and chemical properties of the drug AS-IV loaded Nanocellulose-gelatin hydrogel external stent limit graft vein expansion and make the stent biocompatible. We also found it can prevent restenosis by resisting endothelial-to-mesenchymal transition (EndMT) in vitro. It does so by activating autophagy, and AS-IV can enhance this effect both in vivo and in vitro. This study has added to existing research on the mechanism of extravascular stents in preventing restenosis of grafted veins. Furthermore, we have developed a novel extravascular stent for the prevention and treatment of restenosis. This will help optimize the clinical treatment plan of external stents and improve the prognosis in patients with vein grafts.

Paclitaxel exerts antiplatelet and antithrombotic activities: Additional benefit from use of paclitaxel-coated balloons and -eluting stents in coronary revascularization and prevention of in-stent restenosis

IntroductionPaclitaxel is a microtubule-stabilizing drug used to treat several types of cancer, including ovarian and breast cancer. Because of its antiproliferative effect on vascular smooth muscle cells, balloons and stents are coated with paclitaxel for use in coronary revascularization and prevention of in-stent restenosis (ISR). However, mechanisms underlying ISR are complicated. Platelet activation is one of the major causes of ISR after percutaneous coronary intervention. Although the antiplatelet activity of paclitaxel was noted in rabbit platelets, the effect of paclitaxel on platelets remains unclear. This study investigated whether paclitaxel exhibits antiplatelet activity in human platelets. Methods and resultsPaclitaxel inhibited platelet aggregation induced by collagen but not that induced by thrombin, arachidonic acid, or U46619, suggesting that paclitaxel is more sensitive to the inhibition of collagen-induced platelet activation. Moreover, paclitaxel blocked collagen receptor glycoprotein (GP) VI downstream signaling molecules, including Lyn, Fyn, PLCγ2, PKC, Akt, and MAPKs. However, paclitaxel did not directly bind to GPVI and cause GPVI shedding, as detected by surface plasmon resonance and flow cytometry, respectively, indicating that paclitaxel may interfere with GPVI downstream signaling molecules, such as Lyn and Fyn. Paclitaxel also prevented granule release and GPIIbIIIa activation induced by collagen and low convulxin doses. Moreover, paclitaxel attenuated pulmonary thrombosis and delayed platelet thrombus formation in mesenteric microvessels without significantly affecting hemostasis. ConclusionPaclitaxel exerts antiplatelet and antithrombotic effects. Thus, paclitaxel may provide additional benefits beyond its antiproliferative effect when used in drug-coated balloons and drug-eluting stents for coronary revascularization and prevention of ISR.

Prevention of in-stent restenosis with drug-eluting balloons in patients with postirradiated carotid stenosis accepting percutaneous angioplasty and stenting

ObjectiveTo investigate the technical safety and outcome of in-stent restenosis (ISR) prevention with drug-eluting balloon (DEB) in patients with postirradiated carotid stenosis (PIRCS) undergoing percutaneous angioplasty and stenting (PTAS).MethodsBetween 2017...

Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts

AimsThe aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts. MethodsHSV grafts (n = 10) obtained from patients undergoing CABG were incubated with 30 mM glucose and/or 10 μM pioglitazone or 0.1 % DMSO for 24 h after endothelium removal. ROS levels were examined by chemiluminescence assay, MMP-2,-9,-14, TIMP-2, and α-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, prostaglandin F2α and papaverine was assessed in HSVs. ResultsHG induced superoxide anion (SA) (123 %) and other ROS levels (159 %), up-regulated MMP-2 expression (180 %)/activity (79 %), MMP-14 expression (24 %) and MMP-9 activity while down-regulating TIMP-2 expression (27 %). HG elevated total MMP-2/TIMP-2 ratio (483 %) and MMP-14/TIMP-2 ratio (78 %). However, HG plus pioglitazone inhibited SA (30 %) and other ROS levels (29 %), down-regulated MMP-2 expression (76 %)/activity (83 %), MMP-14 expression (38 %) and MMP-9 activity, while reversing TIMP-2 expression (44 %). HG plus pioglitazone decreased total MMP-2/TIMP-2 ratio (91 %) and MMP-14/TIMP-2 ratio (59 %). HG impaired contractions to all agents but pioglitazone improved them. ConclusionsPioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG.

Иммунный статус в развитии рестеноза у пациентов с окклюзионно-стенотическим поражением бедренно-подколенного артериального сегмента после бедренно-подколенного шунтирования

Objective: to assess the immune status of systemic and local blood flow after femoral-popliteal bypass surgery in patients with and without restenosis. Materials and methods. The analysis of the treatment of 82 patients who underwent femoral-popliteal bypass surgery was carried out. Depending on the condition of the reconstruction zone after 12 months, the patients were divided into two groups: group I - 21 patients without restenosis, group II - 61 patients with the development of restenosis. The analysis of IgA, IgM, IgG, circulating immune complexes (CIC), interleukin (IL)-6, IL-1 in the systemic and local blood flow before and after surgery was performed. Results. In patients with the development of restenosis of the reconstruction zone, the level of IgA in the systemic and IgA, IgM in the local bloodstream was initially lower, the level of CIC, IL-1, IL-6 in the systemic and IgG, IL-1, IL-6 in the local bloodstream was higher, after surgery, the level of IgA in the local bloodstream was lower, higher - IgM in systemic and IL-6 in local blood flow in comparison with patients without restenosis. The correlation between the immune status and the development of restenosis was established: before surgery in the systemic circulation - IgA (r=-0.31, p&lt;0.01), CIC (r=0.39, p&lt;0.001), IL-6 (r=0.25, p&lt;0.05), IL-1 (r=0.26, p&lt;0.05), in the local bloodstream - IgA (r=-0.26, p&lt;0.05), IgM (r=-0.30, p&lt;0.01), IgG (r=0.26, p&lt;0.05), IL-6 (r=0.30, p&lt;0.01), IL-1 (r=0.29, p&lt;0.01); after surgery in the systemic circulation - IgM (r=0.33, p&lt;0.01), in the local - IgA (r=-0.24, p&lt;0.05), IL-6 (r=0.40, p&lt;0.001). The relationship between the degree of chronic arterial insufficiency (r=0.22, p&lt;0.05), the ankle- brachial index after surgery (r=-0.27, p&lt;0.05) with the development of restenosis was revealed. Conclusion. The interrelation of the immune status of the systemic and local blood flow before and after surgery and restenosis in the anastomosis zone after femur-popliteal bypass surgery has been shown. The study of the immune status will make it possible to develop an algorithm for restenosis prevention.

Our experience of using Losartan for esophageal stenosis in children with dystrophic form of congenital epidermolysis bullosa

IntroductionDystrophic epidermolysis bullosa (DEB) is one of the most severe forms of congenital epidermolysis bullosa and characterized by the formation of many surgical complications. Esophageal stenosis is a common complication of DEB and occurs in almost 76% of cases. Balloon dilatation (BD) under X-ray control is the main therapeutic technique, however conservative treatment is necessary to prevent restenosis. The use of the drug losartan is promising due to its antifibrotic effect through the suppression of transforming growth factor-β1 (TGF-β1). PurposeTo evaluate the efficacy of losartan in the prevention of restenosis after BD of esophageal stenosis in children with DEB. Materials and methodsThe study included 19 children from 2 to 16 years old (mean age 9.2 ± 3.58 years) with DEB and X-ray confirmed esophageal stenosis. All children underwent BD. In the main group 9 children after BD have received losartan, in the control group of 10 children - only standard therapy. The observation period was 12 months. ResultsIn the main group, 1 child (11.1%) required repeated dilatation, in the control group - 4 children (40%). Indicators of nutritional deficiency (THINC scale) and the disease severity index (EBDASI) were significantly lower in the group of children treated with losartan. No undesirable actions of the drug were recorded. ConclusionsIn this study losartan showed its safety, contributed to a decrease in the restenosis frequency and an improvement in the nutritional status of children with DEB after BD. However, further studies are required to confirm its effectiveness. Level of EvidenceIV.

Effectiveness of the lateral pedicled endonasal flap for prevention of restenosis in frontal sinus drillouts.

Frontal sinus median drainage according to Draf is an established procedure for achieving maximum drainage of the frontal sinus. Despite great efforts and several modifications, restenosis of the neo-ostium is still a persistent problem. This study presents an approach by implementing local mucosal flaps to prevent restenosis and compares it with the conventional technique without using the flap. Description of endonasal, lateral pedicle mucosal flap. A Draf III procedure was performed on 156 patients between 2012 and 2021. Data for 123 of the included patients were retrospectively analyzed in terms of surgical indication, technique, postoperative aftercare and patency of the drainage pathway. The follow-up observation period was between 3 and 24 months. Treatment with the pedicle mucosal flap took place in 86 cases. 37 patients were treated as a control group without this flap. The analysis showed a significant association to the event &quot;total closure of the drainage pathway&quot; for surgical technique, as well as in the case of the presence of an allergy and the existence of Samter's triad. Furthermore, there was a significant association between the onset of &quot;near total closure of the frontal sinus ostium&quot; and Samter';s triad, CRS and revision surgery was involved. Use of an endonasal lateral pedicle flap for reconstruction of mucosal defects in frontal sinus surgery improves the long-term chances of a patent drainage pathway. Bone exposed by drilling was covered with a local mucosal flap for a faster epithelialization, healing and less scarring.

Laser Microperforation Assisted Drug-Elution from Biodegradable Films.

In a modern high-tech medicine, drug-eluting polymer coatings are actively used to solve a wide range of problems, including the prevention of post-surgery infection, inflammatory, restenosis, thrombosis and many other implant-associated complications. For major assumptions, the drug elution mechanism is considered mainly to be driven by the degradation of the polymer matrix. This process is very environmentally dependent, unpredictable and often leads to a non-linear drug release kinetic. In the present work, we demonstrate how the laser microperforation of cargo-loaded biodegradable films could be used as a tool to achieve zero-order release kinetics with different elution rates. The effects of the laser-induced hole’s diameter (10, 18, 22, 24 µm) and their density (0, 1, 2, 4 per sample) on release kinetic are studied. The linear dynamics of elution was measured for all perforation densities. Release rates were estimated to be 0.018 ± 0.01 µg/day, 0.211 ± 0.08 µg/day, 0.681 ± 0.1 µg/day and 1.19 ± 0.12 µg/day for groups with 0, 1, 2, 4 microperforations, respectively. The role of biodegradation of the polymer matrix is reduced only to the decomposition of the film over time with no major influence on elution rates.

Comparative Analysis With Modified Inclined Technique for Posterior Endoscopic Cervical Foraminotomy in Treating Cervical Osseous Foraminal Stenosis: Radiological and Midterm Clinical Outcomes.

ObjectiveWe compared the midterm clinical and radiological outcomes between 2 types of full endoscopic posterior cervical foraminotomy, including conventional posterior endoscopic cervical foraminotomy (PECF) and modified inclined technique for PECF. MethodsOne of the 2 types of PECF surgery was performed for defined cervical foraminal stenosis. The foraminal expansion ratio and facet resection rate and foraminal stenosis grade were measured using magnetic resonance imaging. Visual analogue scale (VAS) scores for neck and arm pain, neck disability index, MacNab criteria, operation time, hospital stay, and complications, including postoperative dysesthesia, were assessed. Clinical and radiological parameters were compared between the 2 surgical groups. ResultsThere were 49 and 46 patients in the PECF and modified-PECF groups, respectively. The modified-PECF group showed significantly higher expansion of distal foraminal diameter and foraminal height, and a lower facet resection rate compared to PECF group (in all, p<0.001). The modified-PECF group displayed significantly lower VAS score for neck pain at 1 day and 1 week after surgery and lower arm pain VAS score after 6-month follow-up (p=0.002, p=0.001, p=0.002, respectively). ConclusionCompared with the PECF, the modified inclined technique has radiologic benefits, including enhanced facet joint preservation, restoration of the natural course of nerve roots, and prevention of restenosis by expanding the superior articular process base, especially in grade 2 foraminal stenosis. Furthermore, the modified inclined technique significantly improved the postoperative VAS score for neck pain within the 1-week follow-up and that of arm pain after 6-month follow-up.

Iron corroded granules inhibiting vascular smooth muscle cell proliferation.

In-stent restenosis after interventional therapy remains a severe clinical complication. Current evidence indicates that neointimal hyperplasia induced by vascular smooth muscle cell (VSMC) proliferation is a major cause of restenosis. Thus, inhibiting VSMC proliferation is critical for preventing in-stent restenosis. The incidence of restenosis was reduced in nitrided iron-based stents (hereafter referred to as iron stents). We hypothesized that the corroded granules produced by the iron stent would prevent in-stent restenosis by inhibiting VSMC proliferation. To verify this hypothesis, we introduced a dynamic circulation device to analyze the components of corroded granules. To investigate the effects of corroded granules on VSMC proliferation, we implanted the corroded iron stent into the artery of the atherosclerotic artery stenosis model. Moreover, we explored the mechanism underlying the inhibition of VSMC proliferation by iron corroded granules. The results indicated that iron stent produced the corroded granules after implantation, and the main component of the corrosion granules was iron oxide. Remarkably, the corroded granules reduced the neointimal hyperplasia in an atherosclerotic artery stenosis model, and iron corroded granules decreased the neointimal hyperplasia by inhibiting VSMC proliferation. In addition, we revealed that corroded granules reduced VSMC proliferation by activating autophagy through the AMPK/mTOR signaling pathway. Importantly, safety of iron corroded granules was evaluated and proved to be satisfactory hemocompatibility in rabbit model. Overall, the role of corroded granules in restenosis prevention was described for the first time. This finding highlighted the implication of corroded granules produced by iron stent in inhibiting VSMC proliferation, pointing to a new direction to prevent in-stent restenosis.

A Biocompatibility Study of Plasma Nanocoatings onto Cobalt Chromium L605 Alloy for Cardiovascular Stent Applications.

The objective of this study was to evaluate the biocompatibility of trimethylsilane (TMS) plasma nanocoatings modified with NH3/O2 (2:1 molar ratio) plasma post-treatment onto cobalt chromium (CoCr) L605 alloy coupons and stents for cardiovascular stent applications. Biocompatibility of plasma nanocoatings was evaluated by coating adhesion, corrosion behavior, ion releasing, cytotoxicity, and cell proliferation. Surface chemistry and wettability were studied to understand effects of surface properties on biocompatibility. Results show that NH3/O2 post-treated TMS plasma nanocoatings are hydrophilic with water contact angle of 48.5° and have a typical surface composition of O (39.39 at.%), Si (31.92 at.%), C (24.12 at.%), and N (2.77 at.%). The plasma nanocoatings were conformal to substrate surface topography and had excellent adhesion to the alloy substrates, as assessed by tape test (ASTM D3359), and showed no cracking or peeling off L605 stent surfaces after dilation. The plasma nanocoatings also improve the corrosion resistance of CoCr L605 alloy by increasing corrosion potential and decreasing corrosion rates with no pitting corrosion and no mineral adsorption layer. Ion releasing test revealed that Co, Cr, and Ni ion concentrations were reduced by 64–79%, 67–69%, and 57–72%, respectively, in the plasma-nanocoated L605 samples as compared to uncoated L605 control samples. The plasma nanocoatings showed no sign of cytotoxicity from the test results according to ISO 10993-05 and 10993-12. Seven-day cell culture demonstrated that, in comparison with the uncoated L605 control surfaces, the plasma nanocoating surfaces showed 62 ± 7.3% decrease in porcine coronary artery smooth muscle cells (PCASMCs) density and had comparable density of porcine coronary artery endothelial cells (PCAECs). These results suggest that TMS plasma nanocoatings with NH3/O2 plasma post-treatment possess the desired biocompatibility for stent applications and support the hypothesis that nanocoated stents could be very effective for in-stent restenosis prevention.

Risk Factors for Carotid Restenosis in Patients After Eversion Endarterectomy vs Stenting: A Single-Center Experience.

The primary aim of the presented study is to analyze and compare the rate of carotid restenosis in patients after eversion carotid endarterectomy (eCEA), primary carotid angioplasty and stenting (CASp), and stenting for carotid artery restenosis after previous eCEA (CASr). The secondary aim is to compare clinical outcomes in patients with carotid restenosis. The total number of patients with evident carotid restenosis was 223 (24.8%). In patients with eCEA, significant carotid restenosis rate was 12.7%, in the CASp group 18.7%, and CASr 6.7%. Patients with carotid restenosis were asymptomatic in 95.1% of cases. Patients in the CASp group experienced transient ischemic attack more than patients with eCEA (P = .007), while no difference was observed regarding cerebrovascular insult (CVI). The incidence of carotid restenosis was higher in CASp patients, and increased during the follow-up. The majority of patients are asymptomatic post-procedural and the degree of carotid restenosis does not correlate with the occurrence of postoperative symptoms. High low-density lipoprotein cholesterol (LDL-C) levels, low high-density lipoprotein cholesterol (HDL-C) levels, smoking, and a history of vascular surgery correlate with higher degrees of carotid restenosis. The most important factor in the prevention of carotid restenosis is risk factor control as well as adequate pharmacological therapy.

Carotid endarterectomy accompanied by radium- 224 patch angioplasty- mediated diffusing alpha-emitters radiation therapy (DaRT) for restenosis prevention

Background and Aims : Patch angioplasty in conventional carotid endarterectomy is suggested to reduce the risk of restenosis and recurrent ipsilateral stroke compared with primary closure. Diffusing alpha-emitters radiation therapy (DaRT) is a new treatment modality, which utilizes seeds embedded with a low activity of radium- 224 (224Ra). Each seed continuously emits the short-lived alpha particles, which spread over several mm around it, creating a 'apoptotic region' of high alpha-particle dose.

Exosomes Derived from AT2R-Overexpressing BMSC Prevent Restenosis After Carotid Artery Injury by Attenuating the Injury-Induced Neointimal Hyperplasia

Restenosis is a severe complication after percutaneous transluminal coronary angioplasty which limits the long-term efficacy of the intervention. In this study, we investigated the efficiency of exosomes derived from AT2R-overexpressing bone mesenchymal stem cells on the prevention of restenosis after carotid artery injury. Our data showed that AT2R-EXO promoted the proliferation and migration of vascular endothelial cells and maintained the ratio of eNOS/iNOS. On the contrary, AT2R-EXO inhibited the proliferation and migration of vascular smooth muscle cells. In vivo study proved that AT2R-Exo were more effectively accumulated in the injured carotid artery than EXO and Vehicle-EXO controls. AT2R-EXO treatment could improve blood flow of the injured carotid artery site more effectively. Further analysis revealed that AT2REXO prevents restenosis after carotid artery injury by attenuating the injury-induced neointimal hyperplasia. Our study provides a novel and more efficient exosome for the treatment of restenosis diseases after intervention.

3D printed personalized, heparinized and biodegradable coronary artery stents for rabbit abdominal aorta implantation

Biodegradable stents have become the focus of attention in the field of interventional medicine. Compared to non-biodegradable stents, these stents are designed to degrade, leaving behind regenerating healthy arteries. In addition to biodegradability, customizability and anticoagulation are also important for stent treatments. The combination of magnetic resonance angiography (MRA) and 3D printing can customize coronary stents according to different vascular geometries of patients. Therefore, this work focused on the rapid fabrication of stents composed of polycaprolactone (PCL) by 3D printing and then functionalized the stents with heparin via covalent grafting. The 3D printed stents were implanted into the abdominal aorta of rabbits to evaluate the feasibility of implantation and biocompatibility. Mechanical tests showed that 3D printed stents have good mechanical properties. In vitro data demonstrated that the stents had excellent blood compatibility and cytocompatibility. The heparinized PCL(PCL-NH2-Hep) stent can promote the adhesion, spreading and proliferation of human umbilical vein endothelial cells (HUVECs) and inhibit the excessive proliferation of smooth muscle cells (SMCs). Presently, there is insufficient study about 3D printed stent implantation in rabbit arteries. Hence, personalized stents were prepared via MRA and 3D printing, which tailored to the patient's unique anatomy. A 3D printed stent-balloon delivery system was employed to deliver stents to the abdominal aorta. At 3-month follow-up, the PCL-NH2-Hep stent maintained good vascular patency. Moreover, the heparinized stents showed rapid endothelialization and prevention of neointimal restenosis in vivo. This study demonstrated that personalized PCL-NH2-Hep stent may have the potential in the field of biodegradable coronary artery stents.

Restenosis after Coronary Stent Implantation: Cellular Mechanisms and Potential of Endothelial Progenitor Cells (A Short Guide for the Interventional Cardiologist).

Coronary stents are among the most common therapies worldwide. Despite significant improvements in the biocompatibility of these devices throughout the last decades, they are prone, in as many as 10–20% of cases, to short- or long-term failure. In-stent restenosis is a multifactorial process with a complex and incompletely understood pathophysiology in which inflammatory reactions are of central importance. This review provides a short overview for the clinician on the cellular types responsible for restenosis with a focus on the role of endothelial progenitor cells. The mechanisms of restenosis are described, along with the cell-based attempts made to prevent it. While the focus of this review is principally clinical, experimental evidence provides some insight into the potential implications for prevention and therapy of coronary stent restenosis.