Gene transfer of beta-adrenergic signaling components for heart failure.
Heart failure represents one of the leading causes for morbidity and mortality in this country. Despite advances in clinical management, no significant improvements in prognosis have been achieved. Heart failure itself represents a final common endpoint for several disease entities, including hypertension, coronary artery disease, and cardiomyopathy. However, certain biochemical features remain common to the failing myocardium. Foremost among these are alterations in the beta-adrenergic receptor signaling system including G protein and associated regulatory proteins. Recent advances in myocardial transgenic and gene transfer techniques have supported the hypothesis that, on a molecular level, the beta-adrenergic receptor system is a viable therapeutic target for the treatment of heart failure. In this review, we will discuss the biochemical changes that accompany heart failure as well as corresponding novel therapeutic strategies that were uncovered by studies in transgenic mice as well as with beta-adrenergic receptor based gene therapy studies in larger animals.
Koch
Walter J
WJ
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology; D015316:Genetic Therapy; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins