Functional consequences of altering myocardial adrenergic receptor signaling

From the ability to successfully manipulate the mouse genome has come impor tant transgenic and gene-targeted knockout models that impact many areas of biomedical research. Genetically engineered mouse models geared toward the study of cardiovascular regulation have recently been described and provid e powerful tools to study normal and compromised cardiac physiology. The ge netic manipulation of the adrenergic receptor (AR) signaling system in the heart, including its regulation by desensitizing kinases, has shed light on the role of this signaling pathway in the regulation of cardiac contractil ity. One major finding, supported by several mouse models, is that in vivo contractility can be enhanced via alteration of myocardial AR signaling. Th us genetic manipulation of this critical receptor system in the heart repre sents a novel therapeutic approach for improving function of the failing he art.