Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

Cristi L Galindo,Harold R Garner,Thinh Q Pham,Jing Li,Michael A Skinner,Lauren J Mciver,Mounir Errami,John F Mccormick,Neil M Kumar,David A Watson,L Danielle Olson

doi:10.1186/1472-6793-9-23

Abstract

BackgroundIsoproterenol-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.ResultsWe 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.ConclusionThe 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.

Highlights

Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease
Hearts were visibly larger, after ISO-treatment, as determined by examination of hematoxylin and eosin (H&E) stained cryosections (Fig. 1B-D). While both ISO treatment and exercise induced enlargement of the heart, only the pathological hypertrophy model resulted in an increased heart rate (745 ± 15 beats/min before ISO treatment and 821 ± 16 beats/min after ISO-treatment, p value 0.02, n = 4; Fig. 2A)
ISO is mainly used as a cardiac hypertrophy model because it is convenient and yields rapid and reproducible results, but very little is known regarding the precise mechanism of action of this drug or exactly how it induces cardiomyopathy [7]

Summary

Introduction

Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. Regional hypertrophy can result as a consequence of myocardial infarction in response to ischemic heart failure. The disease has multiple specific etiologies, and much research has been performed to elucidate some of the multiple molecular pathways important in the development of myocardial failure [4,5]. Many animal models of cardiac failure have been devised, and they have played an important role in understanding this complicated disease [6]. In many cases the specific method of inducing heart failure in animals does not obviously correlate with common human diseases [7]

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Results

Discussion

Conclusion