Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting
Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting
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DOI：
10.1097/01.tp.0000261109.97928.9c
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发表时间：
2007-05-15
期刊：
影响因子：
6.2
通讯作者：
Plissonnier, Didier
中科院分区：
文献类型：
--
作者：
Freguin-Bouilland, Caroline;Alkhatib, Bassam;Plissonnier, Didier
背景。岩藻多糖是一种新的低分子量硫酸酸化多糖（LMWF），先前已被证明通过刺激基质衍生因子(SDF)-1的释放来动员骨髓源性祖细胞。动员祖细胞被认为可以修复免疫介导的内皮损伤后的内膜病变，从而防止内膜增殖。本研究的目的是评价低分子水分子对移植动脉硬化大鼠同种异体主动脉移植模型的治疗效果。在Brown Norway （BN，供体）和Lewis （Lew，受体）大鼠中进行主动脉移植。受体大鼠给予LMWF （5 mg/kg/d）治疗，30 d处死。为了确定SDF-1在介导LMWF作用中的作用，我们使用了SDF-1受体CXCR4的特异性抑制剂AMD 3100 （20 μ g/kg/day）。通过形态计量学（组织化学）分析对移植段进行评价。未经治疗的同种异体主动脉移植物表现出严重的内膜增生，表明TA。相比之下，与对照组相比，LMWF治疗可显著阻止同种异体移植物内膜增殖（5.7 +/- 3 vs. 66.2 +/- 6 μ m, P < 0.01），并使内膜/中膜比正常化（0.1 +/- 0.1 vs. 1.7 +/- 0.3, P < 0.01）。此外，LMWF治疗刺激同种异体移植物再内皮化，如强内膜内皮一氧化氮合酶抗体和CD31信号所证明。出乎意料的是，AMD治疗未能阻止低分子白细胞f对内膜增厚的保护作用，而单独治疗AMD可减少同种异体移植物的内膜增殖。我们发现，低分子白细胞f治疗减少了内膜厚度，并诱导血管移植物在30天内出现内皮细胞衬里。我们的研究结果可能为预防TA提供一种新的治疗策略。
Background. Fucoidan, a new low molecular weight sulfated polysaccharide (LMWF), has previously been shown to mobilize bone marrow-derived progenitors cells via stimulation of stromal derived factor (SDF)-1 release. Mobilized progenitor cells have been suggested to repair intimal lesions after immune-mediated endothelial injury and thus prevent intimal proliferation. The aim of this study was to evaluate the effect of LMWF treatment in a rat aortic allograft model of transplant arteriosclerosis (TA).Methods. Aortic grafts were performed in Brown Norway (BN, donor) and Lewis (Lew, recipient) rats. The recipient rats were treated with LMWF (5 mg/kg/day) and sacrificed at 30 days. To determine the role of SDF-1 in mediating the effects of LMWF, a specific inhibitor of the SDF-1 receptor CXCR4, AMD 3100 (20 mu g/kg/day), was used. The grafted segments were evaluated by morphometric (histochemical) analyses.Results. Untreated aortic allografts exhibited severe intimal proliferation, indicative of TA. In contrast, LMWF treatment significantly prevented allograft intimal proliferation as compared with controls (5.7 +/- 3 vs. 66.2 +/- 6 mu m, P < 0.01) and permitted a normalization of the intima/media ratio (0.1 +/- 0.1 vs. 1.7 +/- 0.3, P < 0.01). Further, LMWF treatment stimulated allograft reendothelialization, as evidenced by strong intimal endothelial nitric oxide synthase antibody and CD31 signals. Unexpectedly, AMD treatment failed to prevent the protective effect of LMWF on intimal thickening and AMD treatment alone was found to reduced intimal proliferation in allografts.Conclusions. We found that LMWF treatment reduced intimal thickness and induced the presence of an endothelial cell lining in the vascular graft at 30 days. Our findings may suggest a novel therapeutic strategy in the prevention of TA.