Gene expression profiling of α_1b-adrenergic receptor-induced cardiac hypertrophy by oligonucleotide arrays

Objective: Cardiac hypertrophy is closely associated with the development of cardiomyopathies that lead to heart failure. The α_1B adrenergic receptor (α₁-AR) is an important regulator of the hypertrophic process. Cardiac hypertrophy induced by systemic overexpression of the α_1b-AR in a mouse model does not progress to heart failure. We wanted to explore potential gene expression differences that characterize this type of hypertrophy that may identify genes that prevent progression to heart failure. Methods: Transgenic and normal mice (B6CBA) representing two time points were compared; one at 2-3 months of age before disease manifests and the other at 12 months when the hypertrophy is significant. Age-matched hearts were removed, cRNA prepared and biotinylated. Aliquots of the cRNA was subjected to hybridization with Affymetrix chips representing 12 656 murine genes. Gene expression profiles were compared with normal age-matched controls as the baseline and confirmed by Northern and Western analysis. Results: The non-EST genes could be grouped into five functional classifications: embryonic, proliferative, inflammatory, cardiac-related, and apoptotic. Growth response genes involved primarily Src-related receptors and signaling pathways. Transgenic hearts also had a 60% higher Src protein content. There was an inflammatory response that was verified by an increase in IgG and κ-chained immunoglobulins by western analysis. Apoptosis may be regulated by cell cycle arrest through a p53-dependent mechanism. Cardiac gene expression was decreased for common hypertrophy-inducing proteins such as actin, collagen and GP130 pathways. Conclusions: Our results suggest a profile of gene expression in a case of atypical cardiac hypertrophy that does not progress to heart failure. Since many of these altered gene expressions have not been linked to heart failure models, our findings may provide a novel insight into the particular role that the α_1BAR plays in its overall progression or regression.