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Neointimal Hyperplasia (neointimal + hyperplasia)
Selected AbstractsPostinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+ bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant fusion proteinsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2006D. CHEN Summary.,Background:,Coagulation proteins promote neointimal hyperplasia and vascular remodelling after vessel injury, but the precise mechanisms by which they act in vivo remain undetermined. Objectives:,This study, using an injury model in which the neointima is derived from bone marrow (BM)-derived cells, compared inhibition of tissue factor or thrombin on either BM-derived or existing vascular smooth muscle cells. Methods:,Two transgenic (Tg) mouse strains expressing membrane-tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins driven by an , smooth muscle actin (SMA) promoter were generated (, -TFPI-Tg and , -Hir-Tg) and the phenotype after wire-induced endovascular injury was compared with that in wild-type (WT) controls. Results:,WT mice developed progressive neointimal expansion, whereas injury in either Tg was followed by repair back to a preinjured state. This was also seen when WT mice were reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT BM, in which injury was followed by slowly progressive neointimal expansion. Injection of CD34+ cells from Tg mice into injured WT mice resulted in the accumulation of fusion protein-expressing cells from day 3 onwards and an absence of neointimal hyperplasia in those areas. Conclusions:,Neointimal development after wire-induced endovascular injury in mice was completely inhibited when BM-derived cells infiltrating the damaged artery expressed membrane tethered anticoagulant fusion proteins under an , -SMA promoter. These findings enhance our understanding of the pathological role that coagulation proteins play in vascular inflammation. [source] A Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular GraftsBIOTECHNOLOGY PROGRESS, Issue 3 2007Hyun Jung Lim The major cause of hemodialysis vascular access dysfunction (HVAD) is the occurrence of stenosis followed by thrombosis at venous anastomosis sites due to the aggressive development of venous neointimal hyperplasia. Local delivery of antiproliferative drugs may be effective in inhibiting hyperplasia without causing systemic side effects. We have previously demonstrated that paclitaxel-coated expanded poly(tetrafluoroethylene) (ePTFE) grafts, by a dipping method, could prevent neointimal hyperplasia and stenosis of arteriovenous (AV) hemodialysis grafts, especially at the graft-venous anastomoses; however, large quntities of initial burst release have remained a problem. To achieve controlled drug release, paclitaxel (Ptx)-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-NPs) were prepared by the emulsion-solvent evaporation method and then transferred to the luminal surface and inner part of ePTFE vascular grafts through our micro tube pumping and spin penetration techniques. Scanning electron microscope (SEM) images of various stages of Ptx-PLGA-NPs unequivocally showed that micro tube pumping followed by spin penetration effectively transferred Ptx-PLGA-NPs to the inner part, as well as the luminal surface, of an ePTFE graft. In addition, the in vitro release profiles of paclitaxel demonstrated that this new system achieved controlled drug delivery with a reduced initial burst release. These results suggest that loading of Ptx-PLGA-NPs to the luminal surface and the inner part of an ePTFE graft is a promising strategy to ultimately inhibit the development of venous neointimal hyperplasia. [source] Clinical Use of Sirolimus-Eluting StentsCARDIOVASCULAR THERAPEUTICS, Issue 4 2007Ajay J. Kirtane ABSTRACT Drug-eluting stents, or intracoronary stents that combine the local delivery of antirestenotic pharmacologic therapies while maintaining the mechanical advantage of bare metal stents over balloon angioplasty alone, are a highly complex technology that have profoundly affected the practice of percutaneous coronary intervention over the last 5 years. These devices were designed specifically to treat the neointimal hyperplasia occurring after conventional bare metal stent placement, and have been remarkably successful in this regard. However, recent concerns have been raised regarding the long-term safety of these devices, particularly when used outside of the specific patient and lesion subsets studied in the pivotal randomized trials that led to device approval by regulatory bodies within the United States and abroad. This review aims to present a brief description of the sirolimus-eluting stent device platform and its mechanism of action, followed by an overview of current data regarding efficacy and safety regarding the clinical use of sirolimus-eluting stent technology. [source] Randomized evaluation of two drug-eluting stents with identical metallic platform and biodegradable polymer but different agents (paclitaxel or sirolimus) compared against bare stents: 1-Year results of the PAINT trial,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 5 2009Pedro A. Lemos MD Abstract Objectives: We tested two novel drug-eluting stents (DES), covered with a biodegradable-polymer carrier and releasing paclitaxel or sirolimus, which were compared against a bare metal stent (primary objective). The DES differed by the drug, but were identical otherwise, allowing to compare the anti-restenosis effects of sirolimus versus paclitaxel (secondary objective). Background: The efficacy of novel DES with biodegradable polymers should be tested in the context of randomized trials, even when using drugs known to be effective, such as sirolimus and paclitaxel. Methods: Overall, 274 patients with de novo coronary lesions in native vessels scheduled for stent implantation were randomly assigned (2:2:1 ratio) for the paclitaxel (n = 111), sirolimus (n = 106), or bare metal stent (n = 57) groups. Angiographic follow-up was obtained at 9 months and major cardiac adverse events up to 12 months. Results: Both paclitaxel and sirolimus stents reduced the 9-month in-stent late loss (0.54,0.44 mm, 0.32,0.43 mm, vs. 0.90,0.45 mm respectively), and 1-year risk of target vessel revascularization and combined major adverse cardiac events (P < 0.05 for both, in all comparisons), compared with controls. Sirolimus stents had lower late loss than paclitaxel stents (P < 0.01), but similar 1-year clinical outcomes. There were no differences in the risk of death, infarction, or stent thrombosis among the study groups. Conclusion: Both novel DES were effective in reducing neointimal hyperplasia and 1-year re-intervention, compared to bare metal stents. Our findings also suggest that sirolimus is more effective than paclitaxel in reducing angiographic neointima, although this effect was not associated with better clinical outcomes.© 2009 Wiley-Liss, Inc. [source] "Head-to-head comparison between sirolimus-eluting and paclitaxel-eluting stents in patients with complex coronary artery disease: An intravascular ultrasound study"CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 6 2006FSCAI, Pavel, ervinka MD Abstract Background: The aim of this study was to assess neointimal hyperplasia following sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) implantation in a patients with complex coronary disease. Method: Between January to December 2004, 70 patients were enrolled in this study (SES = 37; PES = 33. The primary objective was to assess the efficacy of SES and PES on neointimal proliferation inhibition in patients with complex coronary lesions by volumetric 3D intravascular ultrasound (IVUS) assessment at six-month follow-up. Results: Baseline clinical, demographic or angiographic characteristics were well balanced in both groups. All procedures as well as hospitalisation were uneventful. The percentage of B2/C lesions in our study was >90% in both groups. The IVUS-assessed in-stent mean neointimal hyperplasia volume was significantly lower in lesions treated with SES compared to PES (4.1 ± 11 mm3 vs. 17.4 ± 23 mm3, p < 0.002) at 6 month follow-up. No difference in both MACE (3.0 versus 6.0%, p = NS) and restenosis (5.4 versus 9.1%, p = NS) were found. The in-segment late loss at six month was 0.26 mm in the SES and 0.48 mm in the PES group (p = NS). Conclusions: The present study showed reduced neointimal proliferation after sirolimuseluting as compared to paclitaxel-eluting stents in patients with complex coronary artery disease. Both SES and PES were associated with low rate of angiographic restenosis or major adverse cardiovascular events. © 2006 Wiley-Liss, Inc. [source] | ||||||||||