Beta-Adrenergic gene therapy for cardiovascular disease.
Gene therapy using in vivo recombinant adenovirus-mediated gene transfer is an effective technique that offers great potential to improve existing drug treatments for the complex cardiovascular diseases of heart failure and vascular smooth muscle intimal hyperplasia. Cardiac-specific adenovirus-mediated transfer of the carboxyl-terminus of the beta-adrenergic receptor kinase (betaARKct), acting as a Gbetagamma-beta-adrenergic receptor kinase (betaARK)1 inhibitor, improves basal and agonist-induced cardiac performance in both normal and failing rabbit hearts. In addition, betaARKct adenovirus infection of vascular smooth muscle is capable of significantly diminishing neointimal proliferation after angioplasty. Therefore, further investigation is warranted to determine whether inhibition of betaARK1 activity and sequestration of Gbetagamma via an adenovirus that encodes the betaARKct transgene might be a useful clinical tool for the treatment of cardiovascular pathologies.
Eckhart
Andrea D
AD
Duke University Medical Center, Durham, North Carolina, USA. koch0002@mc.duke.edu
Koch
Walter J
WJ