Gene expression profiling: Classification of mice with left ventricle systolic dysfunction using microarray analysis*

OBJECTIVE: We tested the hypothesis that a set of differentially expressed genes could be used to classify mice according to cardiovascular phenotype after prolonged catecholamine stress. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: One hundred seventy-three male mice were studied: wild-type (WT) C57, WT FVB, WT B6129SF2/J, and beta2 adrenergic receptor knockout. INTERVENTIONS: Mice of each genotype were randomly assigned to 14-day infusions of isoproterenol (120 microg/g/day) or no treatment. Approximately half of the animals underwent left ventricle pressure volume loop analysis. The remaining animals were killed for extraction of messenger RNA from whole heart preparations for microarray analysis. MEASUREMENTS AND MAIN RESULTS: We observed that WT FVB and beta2 adrenergic receptor knockout mice developed systolic dysfunction in response to continuous catecholamine infusion, whereas WT C57 mice developed diastolic dysfunction. Using these mice as the derivation cohort, we identified a set of 83 genes whose differential expression correlated with left ventricle systolic dysfunction. The gene set was then used to accurately classify mice from a separate group (WT B6129SF2/J) into the cohort that developed left ventricle systolic dysfunction after catecholamine stress. CONCLUSIONS: The differential expression pattern of 83 genes can be used to accurately classify mice according to physiological phenotype after catecholamine stress.