Japanese Circulation Society

IS106: Genetic Manipulation of Beta-adrenergic Signaling in the Failing Heart
Walter J. Koch, Ph.D.

Figure 1. The ß-adrenergic receptor (AR) system in heart failure. In end stage human heart failure, the ß-1 AR mRNA and protein are selectively downregulated, while the ß-2 AR remain the same. The ß-1 and ß-2 receptors are uncoupled, mediated by the beta receptor kinase ßAR kinase (ßARK), a member of the family of G protein coupled receptor kinases. ßARK mRNA protein inactivity is increased about 3-fold in human heart failure, which can lead to the enhanced phosphorylation of ß receptors and the functional uncoupling seen in cardiac disease. (Circulation 1993;87:454-463.)

Reprinted with permission from Lippincott Williams and Wilkins (www.lww.com).