Upregulation of collagens detected by gene array in a model of flow-induced pulmonary vascular remodeling
Upregulation of collagens detected by gene array in a model of flow-induced pulmonary vascular remodeling
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DOI：
10.1152/ajpheart.00292.2001
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发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Jacobs, ER
中科院分区：
文献类型：
--
作者：
Medhora, M;Bousamra, M;Jacobs, ER
我们最近报道了幼猪主动脉肺吻合术引起的局部肺动脉阻力增加、新生内膜病变和内侧增厚。该模型用于研究可能参与肺血管重塑的基因表达的变化，采用高通量 Atlas 人类心血管阵列，该阵列携带相似的 600 个心血管相关 cDNA 序列。数据通过 Northern 分析、蛋白质印迹和组织学检查得到证实。通过使用较低严格度的杂交条件，阵列上的 588 个人类基因中有 56% 在放射自显影后显示出可见信号。大约 10% 具有可见杂交的基因因分流诱导的高流量而改变。细胞外基质和细胞粘附分子是上调基因中代表性最高的一组。据我们所知，我们的数据首次利用跨物种 cDNA 阵列、同源杂交、免疫特异性蛋白和组织学的组合证明了流诱导的基因表达变化。我们的观察结果扩大了肺血管重塑中假定候选基因的列表，并支持跨物种微阵列分析在此类应用中的实用性。
We recently reported localized increased pulmonary arterial resistance, neointimal lesions, and medial thickening induced by aortopulmonary anastomosis in young pigs. This model was used to investigate changes in expression of genes potentially involved in pulmonary vascular remodeling employing a high throughput Atlas Human Cardiovascular Array carrying similar to600 cardiovascular-related cDNA sequences. Data were confirmed by Northern analysis, Western blots, and histological examination. With the use of lower stringency conditions for hybridization, 56% of the 588 human genes on the array showed visible signal after autoradiography. Approximately 10% of the genes with visible hybridization were altered by shunt-induced high flow. Extracellular matrix and cell adhesion molecules were the most highly represented group of upregulated genes. To our knowledge, our data are the first to demonstrate flow-induced changes in gene expression using a combination of cross species cDNA arrays, homologous hybridization, immunospecific protein, and histology. Our observations expand the list of genes as putative candidates in pulmonary vascular remodeling and support the utility of cross-species microarray analysis in such applications.