Mechanisms of disease: beta-adrenergic receptors--alterations in signal transduction and pharmacogenomics in heart failure.
Beta-adrenergic signaling is an important regulator of myocardial function. During the progression of heart failure (HF), a reproducible series of biochemical events occurs that affects beta-adrenergic receptor (beta-AR) signaling and cardiac function. Furthermore, there are pathophysiologic alterations in the expression and regulation of proteins that are regulated by beta-ARs during HF. Analyses of these complex signaling pathways have led to a better understanding of HF mechanisms and the use of beta-adrenergic antagonists, which have notably altered HF-related morbidity and mortality. Despite therapeutic advances that have affected beta-AR signaling, HF remains a leading cause of hospitalization and a principal cause of death in industrialized nations. In this review, we summarize current insights into beta-adrenergic signal-transduction pathways, the best-described beta-AR polymorphisms, and therapies that target the beta-AR pathway in HF.
Feldman
David S
DS
Davis Heart and Lung Research Institute, Division of Cardiology/Medicine, Ohio State University, Columbus, OH 43210, USA. feldman-1@medctr.osu.edu
Carnes
Cynthia A
CA
Abraham
William T
WT
Bristow
Michael R
MR
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta