title: [Gene therapy and benefits in modulating of system beta-adrenergic in cardiac insufficiency].
abstract: Understanding the basic molecular mechanisms that lead to heart failure may allow to define new targets for myocardial gene therapy. In this way, the alterations of the beta-adrenergic signaling that are typically observed in cardiac insufficiency, may be positively modulated by gene manipulation. Both the level and activity of the beta-adrenergic receptor kinase (beta ARK1), a regulatory enzyme that phosphorylates agonist occupied beta-adrenoreceptors, are elevated and account for desensitization of cardiomyocytes to catecholamines. We recently demonstrated that expressing beta ARKct, a peptide which inhibits beta ARK1, allows normalization of contractile function in several animal models of heart failure. This approach may represent a valuable alternative for the treatment of heart failure. The current review summarizes recent studies performed using beta ARKct as a transgene to restore normal beta-adrenergic signaling and improve myocardial function.
authors.affiliation: Département de chirurgie cardio-vasculaire, CHUV, Lausanne, Suisse. hendrik.tevaearai@chuv.hospvd.ch
authors.forename: Hendrik T
authors.initials: HT
authors.lastname: Tevaearai
authors.forename: G Brant
authors.initials: GB
authors.lastname: Walton
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006333:Heart Failure / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D023421:Models, Animal; D010455:Peptides; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D002352:Carrier Proteins; D010455:Peptides; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; C445259:beta-adrenergic receptor kinase inhibitory peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases