The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Alan Dardik - One of the best experts on this subject based on the ideXlab platform.
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inhibition of programmed death 1 decreases Neointimal Hyperplasia after patch angioplasty
Journal of Biomedical Materials Research Part B, 2021Co-Authors: Hualong Bai, Ying Xing, Zhiwei Wang, Peng Sun, Shunbo Wei, Wang Wang, Zhiju Wang, Alan DardikAbstract:Neointimal Hyperplasia remains an obstacle after vascular interventions. Programmed death-1 (PD-1) antibody treatment decreases tumor cell proliferation and secretion of inflammatory factors, and several antineoplastic drugs show efficacy against Neointimal Hyperplasia. We hypothesized that inhibition of PD-1 inhibits Neointimal Hyperplasia in a rat patch angioplasty model. In a rat aorta patch angioplasty model, four groups were compared: the control group without treatment, a single dose of humanized PD-1 antibody (4 mg/kg) injected immediately after patch angioplasty, PD-1 antibody-coated patches, and BMS-1 (PD-1 inhibitor)-coated patches. Patches were harvested (Day 14) and analyzed. After patch angioplasty, PD-1-positive cells were present. Inhibition of PD-1 using both intraperitoneal injection of humanized PD1 antibody as well as using patches coated with humanized PD1 antibody significantly decreased Neointimal thickness (p = 0.0199). There were significantly fewer PD-1 (p = 0.0148), CD3 (p = 0.0072), CD68 (p = 0.0001), CD45 (p = 0.001), and PCNA (p < 0.0001)-positive cells, and PCNA/α-actin dual positive cells (p = 0.0005), in the treated groups. Patches coated with BMS-1 showed similarly decreased Neointimal thickness and accumulation of inflammatory cells. Inhibition of PD-1 using PD-1 antibody or its inhibitor BMS-1 can significantly decrease Neointimal thickness in vascular patches. Inhibition of the PD-1 pathway may be a promising therapeutic strategy to inhibit Neointimal Hyperplasia.
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multiscale patient specific computational fluid dynamics models predict formation of Neointimal Hyperplasia in saphenous vein grafts
Journal of Vascular Surgery Cases and Innovative Techniques, 2020Co-Authors: Francesca Donadoni, Alan Dardik, Cesar Pichardoalmarza, Shervanthi Homervanniasinkam, Vanessa DiazzuccariniAbstract:Abstract Stenosis due to Neointimal Hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers is insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics simulations of flow in the lumen and a biochemical model representing NIH growth mechanisms inside the vessel wall. For all three patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography scans.
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role of hypoxia and metabolism in the development of Neointimal Hyperplasia in arteriovenous fistulas
International Journal of Molecular Sciences, 2019Co-Authors: Nirvana Sadaghianloo, Alan Dardik, Julie Contenti, Nathalie M MazureAbstract:For patients with end-stage renal disease requiring hemodialysis, their vascular access is both their lifeline and their Achilles heel. Despite being recommended as primary vascular access, the arteriovenous fistula (AVF) shows sub-optimal results, with about 50% of patients needing a revision during the year following creation. After the AVF is created, the venous wall must adapt to new environment. While hemodynamic changes are responsible for the adaptation of the extracellular matrix and activation of the endothelium, surgical dissection and mobilization of the vein disrupt the vasa vasorum, causing wall ischemia and oxidative stress. As a consequence, migration and proliferation of vascular cells participate in venous wall thickening by a mechanism of Neointimal Hyperplasia (NH). When aggressive, NH causes stenosis and AVF dysfunction. In this review we show how hypoxia, metabolism, and flow parameters are intricate mechanisms responsible for the development of NH and stenosis during AVF maturation.
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multi scale patient specific computational flow dynamics models predict formation of Neointimal Hyperplasia in saphenous vein grafts
bioRxiv, 2019Co-Authors: Francesca Donadoni, Alan Dardik, Cesar Pichardoalmarza, S Homervanniasinkam, Vanessa DiazzuccariniAbstract:Abstract Bypass occlusion due to Neointimal Hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics (CFD) simulations of flow in the lumen, with a biochemical model representing NIH growth mechanisms inside the vessel wall. For all 3 patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography (CT) scans.
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patient specific multi scale modeling of Neointimal Hyperplasia in vein grafts
Frontiers in Physiology, 2017Co-Authors: Francesca Donadoni, Alan Dardik, Cesar Pichardoalmarza, Matthew Bartlett, S Homervanniasinkam, Vanessa DiazzuccariniAbstract:Neointimal Hyperplasia is amongst the major causes of failure of bypass grafts. The disease progression varies from patient to patient due to a range of different factors. In this paper, a mathematical model will be used to understand Neointimal Hyperplasia in individual patients, combining information from biological experiments and patient-specific data to analyze some aspects of the disease, particularly with regard to mechanical stimuli due to shear stresses on the vessel wall. By combining a biochemical model of cell growth and a patient-specific computational fluid dynamics analysis of blood flow in the lumen, remodeling of the blood vessel is studied by means of a novel computational framework. The framework was used to analyze two vein graft bypasses from one patient: a femoro-popliteal and a femoro-distal bypass. The remodeling of the vessel wall and analysis of the flow for each case was then compared to clinical data and discussed as a potential tool for a better understanding of the disease. Simulation results from this first computational approach showed an overall agreement on the locations of Hyperplasia in these patients and demonstrated the potential of using new integrative modeling tools to understand disease progression.
Prabir Roychaudhury - One of the best experts on this subject based on the ideXlab platform.
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severe venous Neointimal Hyperplasia prior to dialysis access surgery
Nephrology Dialysis Transplantation, 2011Co-Authors: Timmy Lee, Lois J Arend, Mahesh Krishnamoorthy, Yang Wang, Rupak K Banerjee, Rino Munda, Vibha Chauhan, Meenakshi J Mistry, Mahmoud Elkhatib, Prabir RoychaudhuryAbstract:Background. Venous Neointimal Hyperplasia is the most common cause of arteriovenous (AV) fistula and graft dysfunction following dialysis access surgery. However, the pathogenetic impact of pre-existing venous Neointimal Hyperplasia at the time of AV access creation on final clinical success is currently unknown in the setting of advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. The aim of this study was to perform a detailed histological, morphometric, and immunohistochemical analysis of vein specimens in advanced CKD and ESRD patients collected at the time of new vascular access placement. Methods. Vein samples from 12 patients were collected at the time of AV access creation near the site of AV anastomosis. Histological, immunohistochemistry and morphometric studies were performed on these vein samples. Results. Examination of the tissue specimens obtained at the time of surgery showed Neointimal Hyperplasia in 10 of 12 specimens, ranging from minimal to very severe. The majority of cells within the neointima were myofibroblasts with a minority of contractile smooth muscle cells present. Conclusion. Our work represents a detailed description of the morphometric and cellular phenotypic lesions present in the veins of CKD and ESRD patients, prior to dialysis access placement. These studies (i) suggest the future possibility of a new predictive marker (pre-existing venous Neointimal Hyperplasia) for AV dialysis access dysfunction and (ii) open the door for the future development of novel local therapies for optimization of the venous substrate on which the dialysis access is created.
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venopathy at work recasting Neointimal Hyperplasia in a new light
Translational Research, 2010Co-Authors: Alexander S Yevzlin, Prabir Roychaudhury, Timmy Lee, Micah R Chan, Yolanda T Becker, Bryan N BeckerAbstract:Hemodialysis vascular access is a unique form of vascular anastomosis. Although it is created in a unique disease state, it has much to offer in terms of insights into venous endothelial and anastomotic biology. The development of Neointimal Hyperplasia (NH) has been identified as a pathologic entity, decreasing the lifespan and effectiveness of hemodialysis vascular access. Subtle hints and new data suggest a contrary idea—that NH, to some extent an expected response, if controlled properly, may play a beneficial role in the promotion of maturation to a functional access. This review attempts to recast our understanding of NH and redefine research goals for an evolving discipline that focuses on a life-sustaining connection between an artery and vein.
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advances and new frontiers in the pathophysiology of venous Neointimal Hyperplasia and dialysis access stenosis
Advances in Chronic Kidney Disease, 2009Co-Authors: Prabir Roychaudhury, Timmy LeeAbstract:Hemodialysis vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of this vascular access dysfunction is venous stenosis as a result of venous Neointimal Hyperplasia within the perianastomotic region (arteriovenous fistula) or at the graft-vein anastomosis (polytetrafluoroethylene, or PTFE, grafts). There have been few effective treatments to date for venous Neointimal Hyperplasia, in part, because of the poor understanding of the pathogenesis of venous Neointimal Hyperplasia. Therefore, this article will (1) describe the pathology of hemodialysis access stenosis in arteriovenous fistulas and grafts, (2) review and describe both current and novel concepts in the pathogenesis of Neointimal Hyperplasia formation, (3) discuss current and future novel therapies for treating venous Neointimal Hyperplasia, and (4) suggest future research areas in the field of hemodialysis vascular access dysfunction.
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Neointimal Hyperplasia in early arteriovenous fistula failure
American Journal of Kidney Diseases, 2007Co-Authors: Prabir Roychaudhury, Lois J Arend, Jianhua Zhang, Mahesh Krishnamoorthy, Yang Wang, Rupak K Banerjee, Antoine Samaha, Rino MundaAbstract:Background Hemodialysis vascular access dysfunction currently is a huge clinical problem. Although arteriovenous fistulas (AVFs) are the preferred form of permanent dialysis access, they continue to have significant problems with early AVF failure. Although inadequate dilatation of the venous segment was believed to have a role in early AVF failure, the exact pathogenesis of early AVF failure is unknown despite the magnitude of the clinical problem. Study Design Case series. Setting & Participants Hemodialysis patients. Outcomes & Measurements Stenotic venous segments from 4 patients with early AVF failure were subjected to a detailed histological, morphometric, and immunohistochemical analysis. Results All 4 patients had significant luminal stenosis, primarily as a result of eccentric Neointimal Hyperplasia. This was confirmed through morphometric analysis, which documented intima-media area and thickness ratios that were greater than unity. Cellular phenotyping studies showed that the majority of cells within the region of Neointimal Hyperplasia were myofibroblasts, with smaller numbers of contractile smooth muscle cells. Limitations We described only a limited number of specimens. Conclusions We show for the first time that aggressive Neointimal Hyperplasia is present in venous segment specimens from patients with early AVF failure. Future therapies to address this problem will need to target this pathogenetic pathway.
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aggressive venous Neointimal Hyperplasia in a pig model of arteriovenous graft stenosis
Kidney International, 2002Co-Authors: Burnett S. Kelly, Sue C. Heffelfinger, James F Whiting, Mary Ann Miller, Anita Reaves, Janice Armstrong, Ashwath Narayana, Prabir RoychaudhuryAbstract:Aggressive venous Neointimal Hyperplasia in a pig model of arteriovenous graft stenosis. Background Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of well over one billion dollars per annum. Venous Neointimal Hyperplasia characterized by stenosis and subsequent thrombosis, is the major cause of polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem, there are currently no effective therapies for the prevention or treatment of venous Neointimal Hyperplasia in PTFE dialysis grafts. We believe that this is partly due to the lack of a validated large animal model of arteriovenous stenosis that could be used to test out novel interventions. Methods Seven-centimeter PTFE loop grafts were placed between the femoral artery and vein of domestic pigs. The grafts were removed at 2, 4, 7, 14 and 28 days after surgery and subjected to a detailed histological and immunohistochemical examination. Results Significant Neointimal Hyperplasia and venous stenosis developed by 28 days at the graft-vein anastomosis. There was minimal Neointimal Hyperplasia at the graft-artery anastomosis. Venous Neointimal Hyperplasia (VNH) was characterized by ( a ) the presence of smooth muscle cells/myofibroblasts; ( b ) angiogenesis within both the neointima and adventitia; and ( c ) the presence of an active macrophage cell layer lining the PTFE graft material. These results are very similar to the human lesion previously described by us in dialysis patients. Conclusions We have developed and validated a pig model of venous Neointimal Hyperplasia that is very similar to the human lesion. We believe that this is an ideal model in which to test out novel interventions for the prevention and treatment of clinical hemodialysis vascular access dysfunction.
Patrick W Serruys - One of the best experts on this subject based on the ideXlab platform.
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the effect of variable dose and release kinetics on Neointimal Hyperplasia using a novel paclitaxel eluting stent platform the paclitaxel in stent controlled elution study pisces
Journal of the American College of Cardiology, 2005Co-Authors: Patrick W Serruys, Georgios Sianos, Alexandre Abizaid, Jiro Aoki, Peter Den Heijer, Hans Bonnier, Pieter C Smits, Dougal Mcclean, Stefan Verheye, Jorge A BelardiAbstract:Objectives The aim of this study was to evaluate the effect of variable dose and release kinetics of paclitaxel on Neointimal Hyperplasia. Background Conventional paclitaxel-eluting stents use a durable polymer coating as a vehicle for drug delivery. The Conor stent (Conor Medsystems, Menlo Park, California) with intra-strut wells and erodable polymer is specifically designed for drug delivery with programmable pharmacokinetics. Methods Two hundred and forty-four patients with single vessel disease received either a bare metal Conor stent (n = 53) or one of six different release formulations that varied in dose (10 or 30 μg) and elution release kinetics (first order, zero order), direction (abluminal, luminal), and duration (5, 10, and 30 days). End points at six months (bare stent group) and at four months (eluting stent groups) were angiographic late loss and Neointimal tissue volume by intravascular ultrasound and the rate of major adverse cardiac events (MACE). Results The lowest in-stent late loss (0.38 mm, p Conclusions This novel eluting stent platform, using an erodable polymer with complete elution of low doses of paclitaxel, is safe. The inhibition of the in-stent Neointimal Hyperplasia was best in the long release groups.
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persistent inhibition of Neointimal Hyperplasia after sirolimus eluting stent implantation
Acc Current Journal Review, 2003Co-Authors: Muzaffer Degertekin, Patrick W Serruys, David P. FoleyAbstract:Background— Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of Neointimal Hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up. Methods and Results— Fifteen patients with de novo coronary artery disease were treated with 18-mm sirolimus-eluting Bx-Velocity stents (Cordis) loaded with 140 μg sirolimus/cm2 metal surface area in a slow release formulation. Quantitative angiography (QCA) and intravascular ultrasound (IVUS) were performed according to standard protocol. Sirolimus-eluting stent implantation was successful in all 15 patients. During the in-hospital course, 1 patient died of cerebral hemorrhage after periprocedural administration of abciximab, and 1 patient underwent repeat stenting after 2 hours because of edge dissection that led to acute occlusion. Throug...
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persistent inhibition of Neointimal Hyperplasia after sirolimus eluting stent implantation long term up to 2 years clinical angiographic and intravascular ultrasound follow up
Circulation, 2002Co-Authors: Muzaffer Degertekin, David P. Foley, Patrick W Serruys, Kengo Tanabe, Evelyn Regar, Jeroen Vos, Peter Smits, Wim J Van Der Giessen, Marcel Van Den Brand, Pim J De FeyterAbstract:BACKGROUND: Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of Neointimal Hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up. METHODS AND RESULTS: Fifteen patients with de novo coronary artery disease were treated with 18-mm sirolimus-eluting Bx-Velocity stents (Cordis) loaded with 140 microg sirolimus/cm2 metal surface area in a slow release formulation. Quantitative angiography (QCA) and intravascular ultrasound (IVUS) were performed according to standard protocol. Sirolimus-eluting stent implantation was successful in all 15 patients. During the in-hospital course, 1 patient died of cerebral hemorrhage after periprocedural administration of abciximab, and 1 patient underwent repeat stenting after 2 hours because of edge dissection that led to acute occlusion. Through 6 months and up to 2 years of follow-up, no additional events occurred. QCA analysis revealed no significant change in stent minimal lumen diameter or percent diameter stenosis, and 3-dimensional IVUS showed no significant deterioration in lumen volume. In 2 patients, additional stenting was performed because of significant lesion progression remote from the sirolimus-eluting stent. CONCLUSION: Sirolimus-eluting stents showed persistent inhibition of Neointimal Hyperplasia for up to 2 years of follow-up.
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radioactive stents delay but do not prevent in stent Neointimal Hyperplasia
Circulation, 2001Co-Authors: Patrick I Kay, David P. Foley, Alexander J Wardeh, Ken Kozuma, A Marco H Knook, Attila Thury, George Sianos, Willem J Van Der Giessen, Peter C Levendag, Patrick W SerruysAbstract:BACKGROUND: Restenosis after conventional stenting is almost exclusively caused by Neointimal Hyperplasia. Beta-particle-emitting radioactive stents decrease in-stent Neointimal Hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of (32)P radioactive stents with an initial activity of 6 to 12 microCi using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). METHODS AND RESULTS: Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (-0.43+/-0.56 mm; P:=0.028) and in the mean lumen diameter in the stent (-0.55+/-0. 63 mm; P:=0.001); a significant increase in in-stent Neointimal Hyperplasia by IVUS (18.16+/-12.59 mm(3) at 6 months to 27.75+/-11. 99 mm(3) at 1 year; P:=0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. CONCLUSIONS: Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 microCi is not favorable when compared with conventional stenting.
Michael S Conte - One of the best experts on this subject based on the ideXlab platform.
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perivascular delivery of resolvin d1 inhibits Neointimal Hyperplasia in a rabbit vein graft model
Journal of Vascular Surgery, 2018Co-Authors: Evan C Werlin, Anuran Chatterjee, Mian Chen, Giorgio Mottola, Kevin D Lance, Daniel A Bernards, Brian E Sansbury, Matthew Spite, Tejal A Desai, Michael S ConteAbstract:Abstract Objective Inflammation is a key driver of excessive Neointimal Hyperplasia within vein grafts. Recent work demonstrates that specialized proresolving lipid mediators biosynthesized from omega-3 polyunsaturated fatty acids, such as resolvin D1 (RvD1), actively orchestrate the process of inflammation resolution. We investigated the effects of local perivascular delivery of RvD1 in a rabbit vein graft model. Methods Ipsilateral jugular veins were implanted as carotid interposition grafts through an anastomotic cuff technique in New Zealand white rabbits (3-4 kg; N = 80). RvD1 (1 μg) was delivered to the vein bypass grafts in a perivascular fashion, using either 25% Pluronic F127 gel (Sigma-Aldrich, St. Louis, Mo) or a thin bilayered poly(lactic-co-glycolic acid) (PLGA) film. No treatment (bypass only) and vehicle-loaded Pluronic gels or PLGA films served as controls. Delivery of RvD1 to venous tissue was evaluated 3 days later by liquid chromatography-tandem mass spectrometry. Total leukocyte infiltration, macrophage infiltration, and cell proliferation were evaluated by immunohistochemistry. Elastin and trichrome staining was performed on grafts harvested at 28 days after bypass to evaluate Neointimal Hyperplasia and vein graft remodeling. Results Perivascular treatments did not influence rates of graft thrombosis (23%), major wound complications (4%), or death (3%). Leukocyte (CD45) and macrophage (RAM11) infiltration was significantly reduced in the RvD1 treatment groups vs controls at 3 days (60%-72% reduction; P Conclusions Local perivascular delivery of RvD1 attenuates vein graft Hyperplasia without associated toxicity in a rabbit carotid bypass model. This effect appears to be mediated by both reduced leukocyte recruitment and decreased cell proliferation within the graft. Perivascular PLGA films may also impart protection through biomechanical scaffolding in this venous arterialization model. Our studies provide further support for the potential therapeutic role of specialized proresolving lipid mediators such as D-series resolvins in modulating vascular injury and repair.
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perivascular delivery of resolvin d1 inhibits Neointimal Hyperplasia in a rat model of arterial injury
Journal of Vascular Surgery, 2017Co-Authors: Giorgio Mottola, Anuran Chatterjee, Mian Chen, Kevin D Lance, Tejal A Desai, Iris O Siguenza, Michael S ConteAbstract:Objective Lipid mediators derived from omega-3 polyunsaturated fatty acids such as resolvin D1 (RvD1) accelerate the resolution of inflammation and have potential as vascular therapeutics. The objective of this study was to evaluate local perivascular delivery of RvD1 as a means to attenuate Neointimal Hyperplasia in a rat model of arterial injury. Methods Smooth muscle cells were harvested from rat aortas to study the effects of RvD1 on rat arterial vascular smooth muscle cell responses in vitro, with focus on inflammation, proliferation, migration, cytoskeletal changes, and cytotoxicity. The safety and efficacy of perivascular delivery of RvD1 through thin biodegradable three-layered poly(lactic-co-glycolic acid) wraps or 25% Pluronic F127 gels were studied in a rat model of carotid angioplasty. A total of 200 ng of RvD1 was loaded into each construct for perivascular delivery after injury. Morphometric and histologic analyses were performed 3 and 14 days after injury. Results RvD1 attenuated rat arterial vascular smooth muscle cell inflammatory pathways, proliferation, migration, and mitogen-induced cytoskeletal changes in vitro, without evidence of cytotoxicity. RvD1-loaded wraps reduced Neointimal formation after carotid angioplasty by 59% vs no-wrap controls ( P = .001) and by 45% vs vehicle-wrap controls ( P = .002). RvD1-loaded Pluronic gels similarly reduced Neointimal formation by 49% vs no-gel controls ( P = .02) and by 52% vs vehicle-gel controls ( P = .02). No group was associated with infection, thrombosis, or negative vessel remodeling. Wraps were found to be easier to apply than gel constructs. Ki67 proliferation index was significantly lower in RvD1-loaded wrap-treated arteries compared with both no-wrap and vehicle-wrap controls at both 3 and 14 days after injury (65% vs no-wrap group and 70% vs vehicle-wrap group at day 3, 49% vs both control groups at day 14; P P P Conclusions Local perivascular delivery of RvD1 attenuates formation of Neointimal Hyperplasia without associated toxicity in a rat model of carotid angioplasty. This effect is likely due to attenuation of inflammatory pathways as well as decreased arterial smooth muscle cell proliferation and migration.
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d series resolvin attenuates vascular smooth muscle cell activation and Neointimal Hyperplasia following vascular injury
The FASEB Journal, 2013Co-Authors: Takuya Miyahara, Sara J Runge, Anuran Chatterjee, Mian Chen, Giorgio Mottola, Jonathan M Fitzgerald, Charles N Serhan, Michael S ConteAbstract:Recent evidence suggests that specialized lipid mediators derived from polyunsaturated fatty acids control resolution of inflammation, but little is known about resolution pathways in vascular injury. We sought to determine the actions of D-series resolvin (RvD) on vascular smooth muscle cell (VSMC) phenotype and vascular injury. Human VSMCs were treated with RvD1 and RvD2, and phenotype was assessed by proliferation, migration, monocyte adhesion, superoxide production, and gene expression assays. A rabbit model of arterial angioplasty with local delivery of RvD2 (10 nM vs. vehicle control) was employed to examine effects on vascular injury in vivo. Local generation of proresolving lipid mediators (LC-MS/MS) and expression of RvD receptors in the vessel wall were assessed. RvD1 and RvD2 produced dose-dependent inhibition of VSMC proliferation, migration, monocyte adhesion, superoxide production, and proinflammatory gene expression (IC50≈0.1–1 nM). In balloon-injured rabbit arteries, cell proliferation (51%) and leukocyte recruitment (41%) were reduced at 3 d, and Neointimal Hyperplasia was attenuated (29%) at 28 d by RvD2. We demonstrate endogenous biosynthesis of proresolving lipid mediators and expression of receptors for RvD1 in the artery wall. RvDs broadly reduce VSMC responses and modulate vascular injury, suggesting that local activation of resolution mechanisms expedites vascular homeostasis.—Miyahara, T., Runge, S., Chatterjee, A., Chen, M., Mottola, G., Fitzgerald, J. M., Serhan, C. N., Conte, M. S. D-series resolvin attenuates vascular smooth muscle cell activation and Neointimal Hyperplasia following vascular injury.
Alan W Heldman - One of the best experts on this subject based on the ideXlab platform.
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paclitaxel stent coating inhibits Neointimal Hyperplasia at 4 weeks in a porcine model of coronary restenosis
Circulation, 2001Co-Authors: Alan W Heldman, Linda Cheng, Mark G Jenkins, Phillip F Heller, Dongwoon Kim, Melvin Ware, Cynthia Nater, Ralph H Hruban, Banafsheh RezaiAbstract:Background—Despite limiting elastic recoil and late vascular remodeling after angioplasty, coronary stents remain vulnerable to restenosis, caused primarily by Neointimal Hyperplasia. Paclitaxel, a microtubule-stabilizing drug, has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to Neointimal Hyperplasia. We tested whether paclitaxel-coated coronary stents are effective at preventing Neointimal proliferation in a porcine model of restenosis. Methods and Results—Palmaz-Schatz stents were dip-coated with paclitaxel (0, 0.2, 15, or 187 μg/stent) by immersion in ethanolic paclitaxel and evaporation of the solvent. Stents were deployed with mild oversizing in the left anterior descending coronary artery (LAD) of 41 minipigs. The treatment effect was assessed 4 weeks after stent implantation. The angiographic late loss index (mean luminal diameter) decreased with increasing paclitaxel dose (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055, P<0.05) at the hig...
