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Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model.
Wu, Bian; Werlin, Evan C; Chen, Mian; Mottola, Giorgio; Chatterjee, Anuran; Lance, Kevin D; Bernards, Daniel A; Sansbury, Brian E; Spite, Matthew; Desai, Tejal A; Conte, Michael S.
Afiliação
  • Wu B; Department of Surgery and Cardiovascular Research Institute, University of California, San Francisco, Calif.
  • Werlin EC; Department of Surgery and Cardiovascular Research Institute, University of California, San Francisco, Calif.
  • Chen M; Department of Surgery and Cardiovascular Research Institute, University of California, San Francisco, Calif.
  • Mottola G; Department of Surgery and Cardiovascular Research Institute, University of California, San Francisco, Calif.
  • Chatterjee A; Department of Surgery and Cardiovascular Research Institute, University of California, San Francisco, Calif.
  • Lance KD; Department of Bioengineering, University of California, San Francisco, Calif.
  • Bernards DA; Department of Bioengineering, University of California, San Francisco, Calif.
  • Sansbury BE; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
  • Spite M; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
  • Desai TA; Department of Bioengineering, University of California, San Francisco, Calif.
  • Conte MS; Department of Surgery and Cardiovascular Research Institute, University of California, San Francisco, Calif. Electronic address: michael.conte2@ucsf.edu.
J Vasc Surg ; 68(6S): 188S-200S.e4, 2018 12.
Article em En | MEDLINE | ID: mdl-30064835
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Docosa-Hexaenoicos / Artéria Carótida Primitiva / Implante de Prótese Vascular / Neointima / Oclusão de Enxerto Vascular / Veias Jugulares / Anti-Inflamatórios Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Vasc Surg Assunto da revista: ANGIOLOGIA Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Docosa-Hexaenoicos / Artéria Carótida Primitiva / Implante de Prótese Vascular / Neointima / Oclusão de Enxerto Vascular / Veias Jugulares / Anti-Inflamatórios Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Vasc Surg Assunto da revista: ANGIOLOGIA Ano de publicação: 2018 Tipo de documento: Article