Gene array analysis of a rat model of pulmonary arteriovenous malformations after superior cavopulmonary anastomosis
Gene array analysis of a rat model of pulmonary arteriovenous malformations after superior cavopulmonary anastomosis
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DOI：
10.1016/j.jtcvs.2008.02.011
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发表时间：
2008-08-01
影响因子：
6
通讯作者：
Duncan, Brian W.
中科院分区：
文献类型：
--
作者：
Tipps, Russell S.;Mumtaz, Muhammed;Duncan, Brian W.
目的：肺动静脉畸形通常发生在儿童谁经历了cavelimentary为single ventricular physiology.Methods：我们开发了一个大鼠模型cavopulinonary吻合，导致肺动静脉畸形，血管造影和组织学类似的人类条件。我们用这个模型来分析与肺动静脉畸形发展后cavalents.Results：6 Sprague-Dawley大鼠进行右上级cavopulinonary吻合，允许左肺作为对照的基因表达谱。在手术后8个月死亡时从每个肺分离总RNA，并通过使用Affyestival大鼠微阵列RAE 230 2.0基因芯片（Affyestival，Santa Clara，CA）进行比较。与对照组相比，137个基因在腔静脉吻合术后的肺中表现出改变的表达：55个（40%）基因表现出表达增加，82个（60%）基因表现出表达减少。发现了与血管生成和血管重塑相关的基因的调节，包括血管生成素-2、胎盘生长因子、几种基质金属蛋白酶和几种胶原亚型。具有血管活性特性的基因，包括内皮素I和内皮素受体B型，表现出基因表达的改变。转化生长因子β超家族信号通路的几个成员也表现出改变expression.Conclusions：这些基因表达的变化可能有因果关系的影响，肺动静脉畸形，开发后空洞anastornosis。
Objective: Pulmonary arteriovenous malformations commonly develop in children who have undergone a cavopulmonary for single-ventricle physiology.Methods: We developed a rat model of cavopulinonary anastomosis that results in pulmonary arteriovenous malformations that are angiographically and histologically similar to the human condition. We used this model to analyze the gene expression profile associated with pulmonary arteriovenous malformations developing after cavopulmonary anastomosis.Results: Six Sprague-Dawley rats underwent right superior cavopulinonary anastomosis, allowing the left lung to serve as a control. Total RNA was isolated from each lung at death 8 months postoperatively and compared by using the Affymetrix Rat Microarray RAE230 2.0 GeneChip (Affymetrix, Santa Clara, Calif). One hundred thirty-seven genes demonstrated altered expression in the lungs after cavopulinonary anastomosis compared with that seen in the control lungs: 55 (40%) genes demonstrated increased expression, and 82 (60%) genes demonstrated decreased expression. Modulation of genes associated with angiogenesis and vascular remodeling was found, including angiopoietin-2, placental growth factor, several matrix metalloproteases, and several collagen subtypes. Genes with vasoactive properties, including, endothelin I and endothelin receptor type B, demonstrated altered gene expression. Several members of the transforming growth factor beta superfamily signaling pathway also demonstrated altered expression.Conclusions: These changes in gene expression might have causative implications for pulmonary arteriovenous malfonnations thatdevelop after cavopulmonary anastornosis.