Effect of aldosterone on gene expression in the heart

ABSTRACT: Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This experiment investigated of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration using oligonucleotide microarrays and compared to those of the control animals who underwent a sham injection. A novel software tool (CAGED) designed for analysis of temporal microarray experiments using a Bayesian approach was used to identify genes differentially expressed between the aldosterone-injected and control group. CAGED analysis identified twelve genes as having significant differences in their temporal profiles between aldosterone-injected and control groups. All of these genes exhibited a decrease in expression level 1-3 hours after aldosterone injection followed by a brief rebound and a return to baseline. These findings were validated by quantitative RT-PCR. The differentially expressed genes included phosphatases, regulators of steroid biosynthesis, inactivators of reactive oxygen species, and structural proteins. Several of these genes are known to functionally mediate biochemical phenomena previously observed to be triggered by aldosterone administration, such as phosphorylation of ERK1/2. These results provide the first description of cardiac genetic response to aldosterone and identify several potential mediators of known biochemical sequelae of aldosterone administration in the heart. Methods: Male C57BL6 mice were injected with aldosterone 10 mcg/kg (experimental group) or vehicle (control group) at time 0. Five animals were sacrificed at each of the following time points in each group: 0, 0.5, 1, 2, 3, 4, 5, and 12 hours from injection. Hearts were removed and total RNA extracted from the hearts of all five animals at each time point / experimental condition was pooled for gene expression analysis. Keywords: time series

ORGANISM(S): Mus musculus

PROVIDER: GSE3440 | GEO | 2005/11/01

SECONDARY ACCESSION(S): PRJNA93481

REPOSITORIES: GEO