Angiotensin II type 2 receptor-mediated gene expression profiling in human coronary artery endothelial cells

Abstract

Despite intensive investigation, the molecular mechanism by which the angiotensin II type 2 (AT 2) receptor exerts its cellular and physiological actions remains elusive. In the present study, we have used microarray expression analysis to identify genes whose expression was regulated by this receptor and to determine its cellular consequences. Lentiviral vector was used to express the AT 2 receptor in human coronary artery endothelial cells (HCAECs), followed by analysis of expression profiles. We observed ≈5224 genes regulated in an AT 2 receptor ligand-independent manner in HCAECs expressing the AT 2 receptor. In addition, 1235 genes were differentially expressed in response to the AT 2 receptor-specific ligand, CGP42112A. Validity of the expression profiles was demonstrated by real-time reverse-transcriptase polymerase chain reaction quantitation of 5 genes. Because some of these genes could be linked to the regulation of extracellular matrix association, we studied the effect of the AT 2 receptor on cell migration. Expression of the AT 2 receptor resulted in a 2-fold inhibition of HCAEC migration. Taken together, these observations demonstrate that the AT 2 receptor regulates expression of genes relevant to cell migration, protein processing, intracellular signaling, and DNA repair in both ligand-dependent and ligand-independent manners. © 2005 American Heart Association, Inc.