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


RESULTS
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.


CONCLUSIONS
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.
Galindo
Cristi L
CL
McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA. harold.garner@utsouthwestern.edu.
Skinner
Michael A
MA
Errami
Mounir
M
Olson
L Danielle
LD
Watson
David A
DA
Li
Jing
J
McCormick
John F
JF
McIver
Lauren J
LJ
Kumar
Neil M
NM
Pham
Thinh Q
TQ
Garner
Harold R
HR
D000704:Analysis of Variance; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D048429:Cell Size; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010805:Physical Conditioning, Animal / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D007545:Isoproterenol