Galindo Cristi L, Skinner Michael A, Errami Mounir, Olson L Danielle, Watson David A, Li Jing, McCormick John F, McIver Lauren J, Kumar Neil M, Pham Thinh Q, Garner Harold R
McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
BMC Physiol. 2009 Dec 9;9:23. doi: 10.1186/1472-6793-9-23.
Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure.
We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays) representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment.
The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration) in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.
异丙肾上腺素诱导的小鼠心脏肥大已在多项研究中用于模拟人类心脏疾病。在本研究中，我们比较了该模型中心脏的转录反应与其他心力衰竭动物模型的转录反应，以及与患心力衰竭的人类心脏的转录反应。
我们对异丙肾上腺素诱导的心脏肥大小鼠和运动诱导的生理性肥大小鼠的RNA进行了微阵列分析，分别鉴定出在病理性和生理性心脏肥大模型中显著改变的865个和2534个基因。我们将我们的结果与代表各种其他动物模型和四种人类心脏疾病的18个不同微阵列数据集（318个单独阵列）进行比较，鉴定出一组在衰竭心脏中普遍改变的64个基因的规范集。我们还生成了一个成对相似性矩阵来说明动物模型与人类心脏病的相关性，并确定缺血是最类似于异丙肾上腺素治疗的人类病症。
基因表达的总体模式与正常和适应不良性心脏肥大之间观察到的结构和分子差异一致，并支持免疫系统（或免疫细胞浸润）在应激诱导的肥大病理学中的作用。如本文所示的跨研究比较为心脏病的进一步研究提供了可能普遍适用于适应不良性心脏应激的靶点，也是确定哪些动物模型在转录水平上最能重现人类疾病的一种手段。
