Proliferation Patterns in a Pig Model of AV Fistula Stenosis: Can we Translate Biology into Novel Therapies?
Proliferation Patterns in a Pig Model of AV Fistula Stenosis: Can we Translate Biology into Novel Therapies?
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DOI：
10.1111/sdi.12240
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发表时间：
2014-11-01
影响因子：
1.6
通讯作者：
Roy-Chaudhury, Prabir
中科院分区：
文献类型：
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作者：
Chan, Jenq-Shyong;Campos, Begona;Roy-Chaudhury, Prabir
动静脉瘘（AVF）狭窄仍然是AVF成熟失败的重要原因，目前尚无有效的治疗方法。为了了解所涉及的机制，我们研究了猪AVF狭窄模型中不同时间点的细胞增殖模式。在第2、7、28和42天进行细胞增殖的免疫组织化学分析。还研究了血管壁不同层内细胞增殖的分布。ANOVA分析用于确定不同时间点和血管壁不同层内细胞增殖幅度之间的差异。外膜增殖发生在第2天，并随着时间的推移而下降。内膜和中膜增殖在第7天达到峰值，然后随着时间的推移而下降。在28天和42天时间点，所有三层中的增殖均极轻微。一个重要的发现是在7天时间点“新生内膜芽”内存在活跃的肌成纤维细胞增殖。结果表明，可能存在早期外膜激活，随后这些细胞进入中膜和内膜层。这些表明，在手术时应用血管周围抗增殖（外膜）治疗可能会减少AVF成熟失败。
Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation failure for which there are currently no effective therapies. To understand the mechanisms involved, we have examined the pattern of cellular proliferation at different time points in a pig model of AVF stenosis. Immunohistochemical analysis of cellular proliferation was performed at 2, 7, 28, and 42 days. The distribution of cellular proliferation within the different layers of the vessel wall was also studied. An ANOVA analysis was used to identify differences between the magnitude of cellular proliferation at different time points and within different layers of the vessel wall. Adventitial proliferation occurred at 2 days and declined over time. Intimal and medial proliferation peaked at 7 days and then decreased over time. There was minimal proliferation in all three layers at the 28- and 42-day time points. An important finding was the presence of active myofibroblast proliferation within "neointimal buds" at the 7-day time point. Results suggest that there could be early adventitial activation, followed by a passage of these cells into the medial and intimal layers. These suggest that the application of perivascular antiproliferative (adventitial) therapies at the time of surgery could potentially reduce AVF maturation failure.