The steroid hormone aldosterone regulates blood pressure by interacting with its receptor, the Mineralocorticoid Receptor (MR) in the kidney. The MR is a ligand-activated transcription factor with clinically available inhibitors that prevent heart attacks, strokes, and cardiovascular mortality in human clinical trials. Our lab is investigating the molecular mechanisms for the protective effects of MR-antagonist drugs using in vitro, cell culture, and state-of-the art transgenic mouse models of vascular disease. We have recently demonstrated that MRs are expressed and regulate gene transcription in vascular cells and that the hormone aldosterone promotes vascular injury and atherosclerosis in mouse models of vascular disease. Our overall hypothesis is that aldosterone acts directly on mineralocorticoid receptors in the blood vessel wall to modulate gene expression in the vessel thereby promoting vascular disease. We have identified the aldosterone-regulated vascular transcriptome and we are exploring the genes, signaling pathways, and vascular functions regulated by aldosterone and MR in the vasculature. These studies are expected to explain the vascular protective effects of MR-antagonist drugs and to identify new drug targets to prevent heart attack and strokes in humans.