Increased venous proinflammatory gene expression and intimal hyperplasia in an aorto-caval fistula model in the rat
Increased venous proinflammatory gene expression and intimal hyperplasia in an aorto-caval fistula model in the rat
复制标题
DOI：
10.1016/s0002-9440(10)64339-8
复制
发表时间：
2003-06-01
影响因子：
6
通讯作者：
Katusic, ZS
中科院分区：
文献类型：
--
作者：
Nath, KA;Kanakiriya, SKR;Katusic, ZS
我们假设动静脉（AV）瘘管的静脉肢体会表现出与血管重塑相关的基因上调，同时伴有新生内膜增生和相关的组织学改变。利用大鼠主动脉-腔室模型和瘘管模型，我们发现在瘘管形成2周后，单核细胞趋化蛋白-1、纤溶酶原激活物抑制剂-1和内皮素-1等促炎基因显著上调。瘘管建立后5周出现不同程度的新生内膜增生，到16周时，新生内膜增生进展明显；在这个时间点，还观察到丰富的细胞外基质。a-平滑肌肌动蛋白染色证实增生性新生内膜中存在平滑肌细胞；超微结构上，平滑肌细胞具有合成和收缩表型。16周时，模型细胞外基质的积累伴随着转化生长因子- β 1 mRNA的表达增加，后者与2周时模型中转化生长因子- β 1 mRNA的抑制形成对比。总之，我们描述了在大鼠房室瘘模型中，促炎基因的显著上调和静脉血管的进行性内膜形成。我们认为，这种基因表达和组织学损伤的改变，加上该模型的相对简单性，为研究诸如血液动力学力响应的差异基因表达、血管重塑过程、静脉旁路移植损伤机制以及血液透析中房室瘘功能障碍机制等及时的生物学和临床相关现象提供了一种新的方法。（中华病理学杂志，2003,32:2079-2090）
We hypothesized that the venous limb of an arteriovenous (AV) fistula would evince up-regulation of genes relevant to vascular remodeling along with neointimal hyperplasia and relevant histological changes. Using the aorto-caval model of an AV, fistula model in the rat, we demonstrate marked up-regulation in such proinflammatory genes as monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and endothelin-1, 2 weeks after the creation of the fistula. Neointimal hyperplasia occurred in variable degrees by 5 weeks after establishing the fistula, and by 16 weeks, such neointimal hyperplasia was progressive and pronounced; at this time point, abundant extracellular matrix was also observed. Smooth muscle cells were present in the hyperplastic neointima as evidenced by staining for a-smooth muscle actin; ultrastructurally, smooth muscle cells with a synthetic as well as a contractile phenotype were readily observed. Accumulation of extracellular matrix in the model at 16 weeks was accompanied by increased expression of transforming growth factor-beta1 mRNA, the latter finding contrasting with the suppression of transforming growth factor-beta1 mRNA observed in this model at 2 weeks. In summary, we describe marked up-regulation in proinflammatory genes and progressive neointimal formation in the venous vasculature in an AV fistula model in the rat. We suggest that such alteration in gene expression and histological injury, in conjunction with the relative simplicity of this model, offer a new approach in the study of such timely biological and clinically relevant phenomena as differential gene expression in response to hemodynamic forces, processes involved in vascular remodeling, mechanisms of injury in venous bypass grafts, and mechanisms of dysfunction of AV fistulae used in hemodialysis. (Am J Pathol 2003, 162:2079-2090)