Evaluated approaches to cardiac in vivo gene therapy
Objective: To investigate the feasibility of cardiac gene therapy
Background: Alterations in the gene expression of calcium regulatory proteins (SERCA, phospholamban) have been demonstrated in a variety of diseases affecting the heart, such as hypertrophy and heart failure, diabetes, and hypothyroidism.
Methods: Mice or rats overexpressing SERCA (sarcoplasmic reticulum Ca2+ ATPase) transgene and wild-type control animals were subjected to experimentally induced pressure overload hypertrophy, diabetes, or hypothyroidism. Cardiac contractile function was evaluated in isolated papillary muscles. In vivo gene therapy was evaluated by injecting adenoviral constructs coding for b-galactosidase or SERCA into the hearts of rats, and studying the function of isolated muscle preparations after several days.
Results: Overexpression of SERCA alleviates the cardiac contractile dysfunction of hypothyroid mice (Cardiovasc. Res. 43: 382-388, 1999. - ABSTRACT). The other studies are still in progress and results have not been published except in abstract form.