Effect of acute aldosterone administration on gene expression profile in the heart.
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 paper describes an investigation 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 with 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 12 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 h 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.
Turchin
Alexander
A
Division of Endocrinology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115, USA. aturchin@partners.org
Guo
Christine Z
CZ
Adler
Gail K
GK
Ricchiuti
Vincent
V
Kohane
Isaac S
IS
Williams
Gordon H
GH
D000450:Aldosterone / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D001499:Bayes Theorem; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000450:Aldosterone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3