Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat model of arterial injury

Wu, Bian; Mottola, Giorgio; Chatterjee, Anushree; Lance, Kevin D.; Chen, Mian; Siguenza, Iris O.; Desai, Tejal A.; Conte, Michael S.

doi:10.1016/j.jvs.2016.01.030

Cited by 49 publications

(65 citation statements)

References 34 publications

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“…30 In a rat model of arterial injury, local perivascular delivery of RvD1 was effective in reducing inflammation and intimal hyperplasia. 31 Here, we demonstrate the safety and efficacy of local perivascular delivery of RvD1 in a rabbit vein graft model. Our results provide further evidence for the vasculoprotective effects of SPMs and suggest their utility in modulating healing after vein bypass grafting.…”

mentioning

confidence: 75%

“…18,36,37 Similar effects have been reported in VSMCs. 18–20,31 Attenuation of growth factor-stimulated VSMC migration by SPMs has been observed in vitro. 17,19–21,31 RvD1 exposure induces cytoskel etal changes in VSMCs corresponding to an antimigratory phenotype, 17,19,31 probably through the cyclic adenosine monophosphate-protein kinase A pathway.…”

Section: Discussionmentioning

confidence: 99%

“…18–20,31 Attenuation of growth factor-stimulated VSMC migration by SPMs has been observed in vitro. 17,19–21,31 RvD1 exposure induces cytoskel etal changes in VSMCs corresponding to an antimigratory phenotype, 17,19,31 probably through the cyclic adenosine monophosphate-protein kinase A pathway. 38 Furthermore, SPMs have shown modest antiproliferative effects on VSMCs both in vitro 19–21,31 and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…38 Furthermore, SPMs have shown modest antiproliferative effects on VSMCs both in vitro 19–21,31 and in vivo. 19,20,31 …”

Section: Discussionmentioning

confidence: 99%

“…19–21,31 The role of inflammation in vein graft disease has been well described. 8,9,39 Trauma during vein harvest and hemodynamic stresses associated with arterialization lead to activation of inflammatory pathways, local expression of cytokines, and infiltration of neutrophils and monocytes.…”

Section: Discussionmentioning

confidence: 99%

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Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model

Werlin

Chen

et al. 2018

Journal of Vascular Surgery

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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 < .01). Cellular proliferation (Ki67 index) was also significantly lower in RvD1-treated vs control grafts at 3 days (40%−50% reduction; P < .01). Treatment of vein grafts with RvD1-loaded gels reduced neointimal thickness at 28 days by 61% vs bypass only (P < .001) and by 63% vs vehicle gel (P < .001). RvD1-loaded PLGA films reduced neointimal formation at 28 days by 50% vs bypass only (P < .001). RvD1 treatment was also associated with reduced collagen deposition in vein grafts at 28 days. 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. (J Vasc Surg 2018;■:1–12.) Clinical Relevance: Autologous vein bypass grafts are the most durable means for revascularization in peripheral vascular disease; however, midterm and long-term outcomes are limited by vein graft hyperplasia with associated vein graft failure. Endogenous proresolving lipid mediators such as resolvin D1 have the potential to attenuate vein graft hyperplasia by accelerating repair. This study provides proof of co...

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mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…38 Furthermore, SPMs have shown modest antiproliferative effects on VSMCs both in vitro 19–21,31 and in vivo. 19,20,31 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model

Werlin

Chen

et al. 2018

Journal of Vascular Surgery

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Biomimetic Nanocarriers of Pro‐Resolving Lipid Mediators for Resolution of Inflammation in Atherosclerosis

Anghelache,

Voicu,

Deleanu

et al. 2023

Adv Healthcare Materials

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Atherosclerosis (ATH) is a systemic disease characterized by a chronic inflammatory process and lipid deposition in the arterial walls. The chronic inflammation within ATH lesions results, at least in part, from the failed resolution of inflammation. This process is controlled actively by specialized pro‐resolving lipid mediators (SPMs), namely lipoxins, resolvins, protectins, and maresins. Herein, biomimetic nanocarriers have been produced comprising a cocktail of SPMs‐loaded lipid nanoemulsions (LN) covered with macrophage membranes (Bio‐LN/SPMs). Bio‐LN/SPMs retained on their surface the macrophage receptors involved in cellular interactions and the “marker of self” CD47, which impeded their recognition and uptake by other macrophages. The binding of Bio‐LN/SPMs to the surface of endothelial cells (EC) and smooth muscle cells (SMC) was facilitated by the receptors on the macrophage membranes and partly by SPMs receptors. In addition, Bio‐LN/SPMs proved functional by reducing monocyte adhesion and transmigration to/through activated EC and by stimulating macrophage phagocytic activity. After intravenous administration, Bio‐LN/SPMs accumulated in the aorta of ApoE‐deficient mice at the level of atherosclerotic lesions. Also, the safety assessment testing revealed no side effects or immunotoxicity of Bio‐LN/SPMs. Thus, the newly developed Bio‐LN/SPMs represent a reliable targeted nanomedicine for the resolution of inflammation in atherosclerosis.This article is protected by copyright. All rights reserved

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Advances in Biomaterials for Drug Delivery

et al. 2018

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Advances in biomaterials for drug delivery are enabling significant progress in biology and medicine. Multidisciplinary collaborations between physical scientists, engineers, biologists, and clinicians generate innovative strategies and materials to treat a range of diseases. Specifically, recent advances include major breakthroughs in materials for cancer immunotherapy, autoimmune diseases, and genome editing. Here, strategies for the design and implementation of biomaterials for drug delivery are reviewed. A brief history of the biomaterials field is first established, and then commentary on RNA delivery, responsive materials development, and immunomodulation are provided. Current challenges associated with these areas as well as opportunities to address long-standing problems in biology and medicine are discussed throughout.

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Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat model of arterial injury

Cited by 49 publications

References 34 publications

Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model

Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model

Biomimetic Nanocarriers of Pro‐Resolving Lipid Mediators for Resolution of Inflammation in Atherosclerosis

Advances in Biomaterials for Drug Delivery

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