Parvalbumin isoforms for enhancing cardiac diastolic function

Diastolic heart failure (DHF), characterized by depressed myocardial relaxation performance and poor ventricular filling, is a distinct form of heart failure accounting for nearly half of the heart failure patients with otherwise normal systolic performance. Defective intracellular calcium (Ca²⁺) cycling is an important mechanism underlying impaired relaxation in DHF. Recently, genetic manipulation of Ca²⁺ handling proteins in cardiac myocytes has been explored for its potential therapeutic application in DHF. Specifically, ectopic expression of the skeletal muscle Ca²⁺ binding protein parvalbumin (Parv) has been shown to accelerate myocardial relaxation in vitro and in vivo. Parv acts as a unique "delayed" Ca²⁺ buffer during diastole by promoting Ca²⁺ transient decay and sequestration and corrects diastolic dysfunction in an energy-independent manner. This brief review summarizes the rationale and development of Parv gene transfer approaches for DHF, and in particular, discusses the divergent effects of Parv isoforms on cardiac myocyte Ca²⁺ handling and contractile function with the long-range goal of alleviating diastolic dysfunction in DHF.