title: Genetic and phenotypic targeting of beta-adrenergic signaling in heart failure.
abstract: Heart failure is a leading cause of hospitalization worldwide. No major significant improvements in prognosis have been achieved for heart failure over the last several decades despite advances in disease management. Heart failure itself represents a final common endpoint for several disease entities, including hypertension and coronary artery disease. On a molecular level, certain biochemical features remain common to failing myocardium. Among these are alterations in the beta-adrenergic receptor (beta-AR) signaling cascade. Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for management of heart failure via genetic manipulation of beta-AR signaling including the targeted inhibition of the beta-AR kinase (betaARK1 or GRK2). In this review, we will discuss the beta-AR signaling changes that accompany heart failure as well as corresponding therapeutic strategies. We will then review the evidence from transgenic mouse work supporting the use of beta-AR manipulation in the failing heart and more recent in vivo applications of gene therapy directed at reversing or preventing heart failure.
authors.affiliation: Centerfor Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. walter.koch@jefferson.edu
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D006333:Heart Failure / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases