Genetic manipulation of beta-adrenergic signalling in heart failure.
Heart failure (HF) represents one of the leading causes for hospitalization in developed nations. Despite advances in the management of coronary artery disease, no significant improvements in prognosis have been achieved for HF over the last several decades. 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 amongst these are alterations in the beta-adrenergic receptor signalling cascade. Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for the management of HF via enhancement of beta-adrenergic signalling. In this review, we will discuss the biochemical changes that accompany HF as well as corresponding therapeutic strategies. We will then review the evidence from transgenic mouse work supporting the use of adrenergic receptor augmentation in the failing heart and more recent in vivo applications of gene therapy directed at reversing or preventing HF.
Davidson
M J
MJ
Department of Surgery, Duke University Medical Center, Durham 27710, USA.
Koch
W J
WJ
D000818:Animals; D015316:Genetic Therapy; D006333:Heart Failure / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D011943:Receptors, Adrenergic, beta