Sustained Release of MiR-217 Inhibitor by Nanoparticles Facilitates MSC-Mediated Attenuation of Neointimal Hyperplasia After Vascular Injury

Mesenchymal stem cells (MSCs) have been proven capable of differentiating into endothelial cells (ECs) and increasing vascular density in mouse ischemia models. However, the therapeutic potential of MSCs in neointimal hyperplasia after vascular injury is still not fully understood. In this study, we proposed that sustained release of miR-217 inhibitor encapsulated by nanoparticles in MSCs can enhance the therapeutic effects of MSCs on alleviating neointimal hyperplasia in a standard mouse wire injury model. We intravenously administered MSCs to mice with injured arteries and examined neointimal proliferation, endothelial differentiation and senescence. We demonstrated that MSCs localized to the luminal surface of the injured artery within 24 h after injection and subsequently differentiated into endothelial cells, inhibited neointimal proliferation and migration of vascular smooth muscle cells. Transfection of MSCs with poly lactic-co-glycolic acid nanoparticles (PLGA-NP) encapsulating an miR-217 agomir abolished endothelial differentiation as well as the therapeutic effect of MSCs. On the contrary, silencing of endogenous miR-217 improved the therapeutic efficacy of MSCs. Our study provides a new strategy of augmenting the therapeutic potency of MSCs in treatment of vascular injury.

Preclinical Evaluation of the Temporary Drug-Coated Spur Stent System in Porcine Peripheral Arteries

Background: Drug penetration into the deeper arterial wall of heavily calcified lesions is one of the limitations of drug-coated balloons and drug-eluting stents in vascular interventions. The Temporary Spur Stent (TSS) system is characterized by a self-expanding nitinol stent that is uniformly covered in radialspikes, which, when coated, should allow a deeper penetration and longer retention of the drug into the diseased artery walls by penetrating through the calcified plaques. Materials and Methods and Results: Uncoated TSS and paclitaxel (PTX)-coated TSS systems have been deployed in porcine peripheral arteries. Four weeks after the deployment of uncoated TSS systems, no adverse vascular remodeling or neointimal formation in the treated vessel segments were noticed. PTX-coated TSS systems transferred 9%±7% of the drug that was on the device to the targeted vessel area (196±163 ng PTX/mg arterial tissue) and the addition of the fluorescent dye Nile red to the coating showed that the spikes promote the transfer of the coating to the deeper layers of the vessel wall. The PTX-coated TSS systems showed a significant reduction in neointimal proliferation compared to the uncoated TSS systems: quantitative angiography showed a vessel diameter stenosis of 37.2%±11.0% and 16.4%±8.8% 4 weeks after the treatment with uncoated and PTX-coated TSS systems, respectively. Conclusion: The treatment with the TSS system was well tolerated and the spikesfacilitate the transfer of the coating into deeper layers of the vessel wall. Moreover, the PTX-coated TSS systems effectively inhibit neointimal proliferation.

Influence of dual antiplatelet therapy duration on neointimal condition after second-generation drug-eluting stent implantation

Guidelines recommend shorter duration (1–12 months) for dual antiplatelet therapy (DAPT) in the second-generation drug-eluting stent (DES) era. However, whether shorter DAPT duration affects stent strut conditions and neointimal characteristics at mid-term follow-up remains uncertain. Therefore, we studied the relation between DAPT duration and vascular healing response as assessed by optical coherence tomography (OCT). This study was retrospective observational study. Participants comprised 64 patients who underwent serial OCT at both 9 and 18 months after DES implantation. All patients received DAPT until the 9-month follow-up then were divided into two groups: 49 patients who continued DAPT (longer DAPT group); and 15 patients who stopped taking the P2Y12 inhibitor and were treated with aspirin alone (shorter DAPT group) at the 18-month follow-up. Using OCT, we evaluated and compared stent strut conditions and neointimal characteristics between groups at both 9 and 18 months after stent implantation. Baseline clinical and procedural parameters were mostly similar between groups. At the 18-month follow-up, no in-stent thrombus assessed by OCT was observed in either group. No significant differences in OCT characteristics or measurements of neointima were seen between groups at 9- or 18-month follow-ups. Neointimal volume increased from 9 to 18 months in both groups, with a similar degree of neointimal proliferation in both groups (shorter DAPT group, 0.23 ± 0.29 mm3/mm; longer DAPT group, 0.19 ± 0.27 mm3/mm; P = 0.56). In conclusion, interrupting DAPT 9 months after second-generation DES implantation did not affect the development of in-stent thrombus, neointimal proliferation or stent strut coverage at 18-month follow-up compared with continuing DAPT.

Abstract 13420: The LDL/apolipoprotein B Ratio Which is an Index for LDL Particle Size is a Strong Predictor for Neointimal Characteristics and In-stent Restenosis After Everolimus-eluting Stent Implantation

Introduction: The smaller size of LDL particle has suggested the development of endothelial dysfunction, atherosclerosis and in-stent restenosis (ISR), but little is known regarding the impact of LDL particle size on neointimal formation leading to ISR. Hypothesis: The LDL-C/Apolipoprotein B (Apo B) ratio < 1.2 has been reported to indirectly represent a high proportion of sdLDL. It was hypothesized that in-stent neointimal proliferation in LDL/ApoB < 1.2 patients may be excessive and unstable. Methods: In 135 patients, we investigated the relationship between the LDL particle size and neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during follow-up angiography after stent implantation. Results: ISR was identified in 35 patients, who had a significantly lower LDL/ApoB ratio (0.99±0.25 vs. 1.17±0.25; p < 0.01) and higher proportion of yellow grade 2 and 3 by CAS than non-ISR group (n=100). Among the non-ISR group, LDL/ApoB < 1.2 group (n=59) had a significantly larger neointimal volume by OCT, and higher proportion of yellow grade 2 and 3 by CAS compared with LDL/ApoB > 1.2 group (n=41) (Figure). Conclusions: Smaller size of LDL strongly associated with the neointimal proliferation, the neointimal instability and ISR evidenced by multimodalities, suggesting that smaller ratio of LDL/ApoB could be a surrogate marker for the neointimal characteristics after stent implantation.

The Ultimaster coronary stent system: 5-year worldwide experience

Newer generation drug-eluting stents have significantly improved outcomes in patients undergoing percutaneous coronary intervention by reducing the risk of restenosis and stent thrombosis. In comparison with first-generation ones, contemporary drug-eluting stents have thinner struts and more biocompatible polymers, which reduce inflammation, promote endothelialization and decrease neointimal proliferation. The Ultimaster™/Ultimaster™ Tansei™ coronary stent system is a cobalt–chromium, biodegradable polymer, sirolimus-eluting stent (Terumo, Tokyo, Japan) that received the Conformitè Européenne mark approval for clinical use in 2014/2018. This device has been the object of intense clinical evaluation in controlled randomized studies and observational registries. In this article, we analytically reviewed the available clinical data with a focus on the latest real-world evidence that demonstrates excellent performance in all of the clinical subsets.

The prognostic value of high-sensitivity C-reactive protein blood level after coronary stenting for the development of stent restenosis

Aim To analyze the relationship between serum concentrations of high-sensitivity C-reactive protein (hsCRP) in dynamics and development of restenosis at 12 months following elective coronary stent placement (CSP).Material and methods The key role in atherogenesis, neointimal proliferation and restenosis belongs to inflammation. This study included 91 patients (median age, 60 [56; 66] years) with stable exertional angina after an elective CSP using second-generation stents. Follow-up coronarography was performed for 60 patients at 12 months. Concentration of hsCRP was measured immediately prior to CSP and at 1, 3, 6, and 12 months after CSP. Restenosis of the stented segment (50% or more narrowing of the stented segment or a 5-mm vessel segment proximally or distally adjacent to the stented segment) was observed in 8 patients.Results According to results of the ROC analysis, the increase in hsCRP concentration >0.9 mg/l (>25%) at one month after CSP had the highest predictive significance with respect of restenosis (area under the ROC curve, 0.89 at 95 % confidence interval (CI) from 0.79 to 0.99; sensitivity, 87.5 %; specificity, 82.8 %; р=0.0005), which was superior to the absolute value of hsCRP concentration >3.0 mg/l (area under the ROC curve, 0.82 at 95 % CI from 0.68 to 0.96; р=0.0007).Conclusion Increased concentration of hsCRP ≥0.9 mg /l (≥25 %) at a month after CSP was associated with restenosis of the coronary artery stented segment.

An Overview of the Design, Development and Applications of Biodegradable Stents

Background & Objectives: Stents have been effectively used in the treatment of vascular diseases and further explorations are going on in treating various strictures including tracheal, intestinal, nasal, urethra and esophageal. Stents serve as a support to walls of the lumen to prevent restenosis. Metal stents prevent in-stent restenosis but the corrosion of the metallic framework causes further complications. To overcome the shortcomings of metallic stents, metallic Drug-Eluting Stents (DES) have been designed where the drugs are chosen as an anti-restenosis agent in such a way that it prevents thrombosis, neointimal proliferation and possess immunosuppressive properties. Biodegradable stents are becoming ideal, provided they effectively spot the target stricture and have long-term stability to support the walls of the body conduit which in turn aids in eliminating the need for a second surgery. Polymeric materials can be used to enhance the mechanical strength and prolong the degradation time of biodegradable DES, thereby making it an ideal choice for stenting. Discussion: This review focus on the progress made in the design, manufacture, characterization studies and applications of stents over the past decade. Conclusion: We concluded that the use of stents is now an emerging technique for the treatment of GI strictures caused due to colorectal cancer, esophageal cancer, cholangiocarcinoma, Crohn’s disease etc. Though BDS have several advantages, advanced techniques are needed for fabrication and suitable modification in the design of the scaffold to enhance its clinical efficacy and to thereby develop an ideal endoprosthetic device.

Diepoxy- Versus Glutaraldehyde-Treated Xenografts: Outcomes of Right Ventricular Outflow Tract Reconstruction in Children

Background: Xenografts used for right ventricular outflow tract (RVOT) reconstruction are typically treated with glutaraldehyde. However, potential benefit of epoxy treatment was demonstrated in experimental studies. We aimed to compare diepoxy-treated bovine pericardial valved conduits (DE-PVCs) and glutaraldehyde-treated bovine pericardial valved conduits (GA-PVCs) for RVOT reconstruction in pediatric patients. Methods: Between 2002 and 2017, 117 patients underwent RVOT reconstruction with PVC in single center: DE-PVC group, n = 39; and GA-PVC group, n = 78. After performing propensity score analysis (1:1) for the entire sample, 29 patients from the DE-PVC group were matched with 29 patients from the GA-PVC group. Results: There were no conduit-related deaths. In the DE-PVC group, the freedom from conduit failure was 90.9% at four years and 54.3% at eight years postoperatively. In the GA-PVC group, it was 46.3% and 33.1%, respectively. The difference was significant ( P = .037). Conduit failure was typically caused by stenosis in both groups. In the DE-PVC group, the main cause of stenosis was xenograft calcification (27.6%); while in the GA-PVC group, it was mostly due to neointimal proliferation (25.0%) and, less often, calcification (14.3%). Conduit thrombosis was the cause of replacement in 6.9% of patients from the GA-PVC group. Conclusions: Diepoxy-treated bovine pericardial valved conduit is a suitable alternative to GA-PVC for RVOT reconstruction in pediatric patients. Diepoxy-treated bovine pericardial valved conduits may be less prone to conduit failure and more resistant to neointimal proliferation and conduit thrombosis than GA-PVCs.