[Gene therapy and benefits in modulating of system beta-adrenergic in cardiac insufficiency]

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.