Angiotensin II Type 2 Receptor–Mediated Gene Expression Profiling in Human Coronary Artery Endothelial Cells

Despite intensive investigation, the molecular mechanism by which the angiotensin II type 2 (AT2) 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 AT2 receptor in human coronary artery endothelial cells (HCAECs), followed by analysis of expression profiles. We observed approximately 5224 genes regulated in an AT2 receptor ligand-independent manner in HCAECs expressing the AT2 receptor. In addition, 1235 genes were differentially expressed in response to the AT2 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 AT2 receptor on cell migration. Expression of the AT2 receptor resulted in a 2-fold inhibition of HCAEC migration. Taken together, these observations demonstrate that the AT2 receptor regulates expression of genes relevant to cell migration, protein processing, intracellular signaling, and DNA repair in both ligand-dependent and ligand-independent manners.