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首页> 外文期刊>Circulation research: a journal of the American Heart Association >Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury.
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Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury.

机译:硝酸脂肪酸抑制腔内血管损伤后新内膜的形成。

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摘要

RATIONALE: Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. OBJECTIVE: The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. METHODS AND RESULTS: The in vivo administration (21 days) of nitro-oleic acid (OA-NO(2)) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO(2) treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals,P<0.0001). Increased heme oxygenase (HO)-1 expression accounted for much of the vascular protection induced by OA-NO(2) in both cultured aortic smooth muscle cells and in vivo. Inhibition of HO by Sn(IV)-protoporphyrin or HO-1 small interfering RNA reversed OA-NO(2)-induced inhibition of platelet-derived growth factor-stimulated rat aortic smooth muscle cell migration. The upregulation of HO-1 expression also accounted for the antistenotic actions of OA-NO(2) in vivo, because inhibition of neointimal hyperplasia following femoral artery injury was abolished in HO-1(-/-) mice (OA-NO(2)-treated wild-type versus HO-1(-/-) mice, P=0.016). CONCLUSIONS: In summary, electrophilic nitro-fatty acids induce salutary gene expression and cell functional responses that are manifested by a clinically significant outcome, inhibition of neointimal hyperplasia induced by arterial injury.
机译:理由:脂肪酸硝基烯烃是一氧化氮和亚硝酸盐依赖性氧化性炎症反应的内源性亲电子副产物。现有证据表明,硝基烯烃支持促进炎症消退的翻译后蛋白质修饰和转录激活。目的:本研究的目的是使用鼠类血管损伤模型评估合成的硝基烯烃的体内给药是否可在体内引发抗炎作用。方法和结果:在小鼠模型(OA-NO(2)治疗)中,体内施用硝酸油酸(OA-NO(2))(21天)抑制了股动脉钢丝损伤后新内膜增生内膜面积和内膜与中膜的比例与用溶媒或油酸(OA)处理的动物相比,P <0.0001)。血红素加氧酶(HO)-1表达增加解释了由OA-NO(2)在培养的主动脉平滑肌细胞和体内产生的大部分血管保护作用。 Sn(IV)-原卟啉或HO-1小干扰RNA抑制HO逆转了OA-NO(2)诱导的对血小板衍生生长因子刺激的大鼠主动脉平滑肌细胞迁移的抑制作用。 HO-1表达的上调也解释了OA-NO(2)在体内的抗狭窄作用,因为在HO-1(-/-)小鼠中(OA-NO(2)取消了股动脉损伤后对内膜增生的抑制作用)处理的野生型小鼠与HO-1(-/-)小鼠相比,P = 0.016)。结论:总的来说,亲电子的硝基脂肪酸可诱导有益的基因表达和细胞功能反应,这在临床上具有重要意义,可抑制动脉损伤引起的内膜增生。

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