Parvalbumin gene transfer corrects diastolic dysfunction in diseased cardiac myocytes

Heart failure frequently involves diastolic dysfunction that is characteriz ed by a prolonged relaxation. This prolonged relaxation is typically the re sult of a decreased rate of intracellular Ca2+ sequestration. No effective treatment for this decreased Ca2+ sequestration rate currently exists. As a n approach to possibly correct diastolic dysfunction, we hypothesized that expression of the Ca2+ binding protein parvalbumin in cardiac myocytes woul d lead to increased rates of Ca2+ sequestration and mechanical relaxation. Parvalbumin. which is normally absent in cardiac tissue, is known to act as a soluble relaxing factor in fast skeletal muscle fibers by acting as a de layed Ca2+ sink. As a test of the hypothesis, gene transfer was used to exp ress parvalbumin in isolated adult cardiac myocytes. We report here that ex pression of parvalbumin dramatically increases the rate of Ca2+ sequestrati on and the relaxation rate in normal cardiac myocytes. Importantly, parvalb umin fully restored the relaxation rate in diseased cardiac: myocytes isola ted from an animal model of human diastolic dysfunction. These findings ind icate that parvalbumin gene transfer offers unique potential as a possible direct treatment for diastolic dysfunction in failing hearts.