Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis
Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis
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DOI：
10.1152/ajpheart.91526.2007
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发表时间：
2008-09-01
影响因子：
4.8
通讯作者：
Bernstein, Daniel
中科院分区：
文献类型：
--
作者：
Urashima, Takashi;Zhao, Mingming;Bernstein, Daniel
右心室（RV）功能障碍是先天性心脏病修补术后患者常见的长期并发症。以前的研究者已经研究了左心室（LV）重塑的细胞和分子机制，但对应激RV知之甚少。我们的目的是提供一个详细的生理特征的模型，RV肥大和失败，包括RV-LV相互作用，并比较基因改变后负荷RV与LV。86只小鼠行肺动脉缩窄术。轻度和中度肺动脉狭窄（PS）的小鼠出现稳定的肥大而无失代偿。重度PS小鼠出现水肿、RV功能下降和高死亡率。组织多普勒成像显示严重PS组的间隔不同步和有害的RV-LV相互作用。微阵列分析显示196个基因表达增加，1,114个基因表达减少。几种转录物在后负荷RV中差异性增加，但在后负荷LV中没有，包括丛生蛋白、成神经细胞瘤致瘤性抑制1、Dkk 3、Sfrp 2、p53结合蛋白、膜联蛋白A7和赖氨酰氧化酶。我们已经表征了RV肥大和衰竭的小鼠模型，为研究RV重塑的生理和分子事件提供了平台。尽管RV和LV对后负荷应激的分子反应大多一致，但存在几个关键差异，这可能代表RV衰竭特异性治疗的靶点。
Right ventricular (RV) dysfunction is a common long-term complication in patients after the repair of congenital heart disease. Previous investigators have examined the cellular and molecular mechanisms of left ventricular (LV) remodeling, but little is known about the stressed RV. Our purpose was to provide a detailed physiological characterization of a model of RV hypertrophy and failure, including RV-LV interaction, and to compare gene alterations between afterloaded RV versus LV. Pulmonary artery constriction was performed in 86 mice. Mice with mild and moderate pulmonary stenosis (PS) developed stable hypertrophy without decompensation. Mice with severe PS developed edema, decreased RV function, and high mortality. Tissue Doppler imaging demonstrated septal dyssynchrony and deleterious RV-LV interaction in the severe PS group. Microarray analysis showed 196 genes with increased expression and 1,114 with decreased expression. Several transcripts were differentially increased in the afterloaded RV but not in the afterloaded LV, including clusterin, neuroblastoma suppression of tumorigenicity 1, Dkk3, Sfrp2, formin binding protein, annexin A7, and lysyl oxidase. We have characterized a murine model of RV hypertrophy and failure, providing a platform for studying the physiological and molecular events of RV remodeling. Although the molecular responses of the RV and LV to afterload stress are mostly concordant, there are several key differences, which may represent targets for RV failure-specific therapy.