Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat model of arterial injury.
Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat model of arterial injury.
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DOI：
10.1016/j.jvs.2016.01.030
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发表时间：
2017-01
影响因子：
4.3
通讯作者：
Conte, Michael S.
中科院分区：
文献类型：
--
作者：
Wu, Bian;Mottola, Giorgio;Chatterjee, Anuran;Lance, Kevin D.;Chen, Mian;Siguenza, Iris O.;Desai, Tejal A.;Conte, Michael S.
来自ω-3多不饱和脂肪酸的脂质介质，如Resolvin D1（RvD 1），可加速炎症的消退，并具有作为血管治疗剂的潜力。本研究的目的是评价局部血管周围递送RvD 1作为减轻大鼠动脉损伤模型中新生内膜增生的手段。从大鼠动脉中收获平滑肌细胞，以研究RvD 1对大鼠动脉血管平滑肌细胞（RASMC）体外反应的影响，重点是炎症、增殖、迁移、细胞骨架变化和细胞毒性。在颈动脉血管成形术的大鼠模型中研究了通过薄的可生物降解的3层PLGA包裹物或25%Pluronic F127凝胶血管周围递送RvD 1的安全性和有效性。将总共200 ng RvD 1加载到每个构建体中，用于损伤后的血管周围递送。伤后3天和14天进行形态学和组织学分析。RvD 1在体外减弱了RASMC的炎症通路、增殖、迁移和有丝分裂原诱导的细胞骨架变化，没有细胞毒性的证据。与无包裹对照组相比，RvD 1装载包裹物减少颈动脉血管成形术后新生内膜形成59%（P = .001），与载体包裹物对照组相比减少45%（P = .002）。与无凝胶对照相比，负载RvD 1的pluronic凝胶同样减少了49%的新生内膜形成（P = 0.02），与溶剂凝胶对照相比减少了52%（P = 0.02）。没有一组与感染、血栓形成或负性血管重塑相关。发现包裹物比凝胶结构更容易应用。在损伤后第3天和第14天，与无包裹物和载体包裹物对照相比，RvD 1负载的包裹物处理的动脉中的Ki 67增殖指数显著更低（在第3天，65%相对于无包裹物组，70%相对于载体包裹物组，在第14天，49%相对于两个对照组，P <0.05）。同样，氧化应激（30%和29%，P < .05）。和NF-kB活化（42%和45%，p<0.05）在负载RvD 1的包裹物组中显著低于无包裹物和载体包裹物对照。在颈动脉血管成形术的大鼠模型中，RvD 1的局部血管周围递送减弱了新生内膜增生的形成，而没有相关的毒性。这种作用可能是由于炎症途径的减弱以及动脉平滑肌细胞增殖和迁移的减少。
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. Smooth muscle cells were harvested from rat aortas to study the effects of RvD1 on rat arterial vascular smooth muscle cell (RASMC) responses in vitro, with focus on inflammation, proliferation, migration, cytoskeletal changes and cytotoxicity. The safety and efficacy of perivascular delivery of RvD1 via thin biodegradable 3-layered PLGA wraps or 25% Pluronic F127 gels were studied in a rat model of carotid angioplasty. A total of 200 ng RvD1 was loaded into each construct for perivascular delivery after injury. Morphometric and histologic analyses were performed 3 and 14 days after injury. RvD1 attenuated RASMC 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% versus no-wrap controls (P = .001) and by 45% versus vehicle-wrap controls (P = .002). RvD1-loaded pluronic gels similarly reduced neointimal formation by 49% versus no-gel controls (P = .02) and by 52% versus 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 to both no-wrap and vehicle-wrap controls at both 3 and 14 days post-injury (65% versus no-wrap group and 70% versus vehicle-wrap group at day 3, 49% versus both control groups at day 14, P < .05). Similarly, oxidative stress (30% and 29%, P < .05). and NF-kB activation (42% and 45%, p<.05) were significantly lower in the RvD1-loaded wrap group compared to both no-wrap and vehicle-wrap controls at three days post-injury 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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影响因子：
64.8
作者：
Chiang, Nan;Fredman, Gabrielle;Backhed, Fredrik;Oh, Sungwhan F.;Vickery, Thad;Schmidt, Birgitta A.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
DOI：
10.1006/bbrc.1995.2204
发表时间：
1995-08-24
影响因子：
3.1
作者：
AUTIERI, MV;YUE, TL;OHLSTEIN, E
通讯作者：
OHLSTEIN, E
影响因子：
7.5
作者：
Finkel, T
通讯作者：
Finkel, T
影响因子：
3.5
作者：
Hirsch, Alan T.;Hartman, Lacey;Virnig, Beth A.
通讯作者：
Virnig, Beth A.
影响因子：
3.7
作者：
Chatterjee A;Sharma A;Chen M;Toy R;Mottola G;Conte MS
通讯作者：
Conte MS