In vivo acceleration of heart relaxation performance by parvalbumin gene delivery
Michael L. Szatkowski, … , Faris P. Albayya, Joseph M. Metzger
Michael L. Szatkowski, … , Faris P. Albayya, Joseph M. Metzger
Published January 15, 2001
Citation Information: J Clin Invest. 2001;107(2):191-198. https://doi.org/10.1172/JCI9862.
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Article

In vivo acceleration of heart relaxation performance by parvalbumin gene delivery

Abstract

Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new in vivo application of parvalbumin, a calcium-binding protein that facilitates ultrafast relaxation of specialized skeletal muscles. Parvalbumin is not naturally expressed in the heart. We show that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. Parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism. Additionally, parvalbumin gene transfer may provide a new therapeutic approach to correct cellular disturbances in calcium signaling pathways that cause abnormal growth or damage in the heart or other organs.

Authors

Michael L. Szatkowski, Margaret V. Westfall, Carlen A. Gomez, Philip A. Wahr, Daniel E. Michele, Christiana DelloRusso, Immanuel I. Turner, Katie E. Hong, Faris P. Albayya, Joseph M. Metzger

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Acceleration of myocardial twitch relaxation rates by parvalbumin. (a) R...
Acceleration of myocardial twitch relaxation rates by parvalbumin. (a) Representative traces of force relaxation in a parvalbumin-treated and a vehicle-treated heart. Force records are normalized to enable direct comparison of relaxation rates between groups. Maximum twitch forces were not different between groups. (b–d) Summaries of one-half relaxation times (1/2 RT) (b), and rate constants for the initial (c) and late (d) phases of relaxation of the cardiac twitch. 1/2 RT is calculated as the time interval from peak twitch force to one-half decay in peak force. Relaxation rate constants were obtained using single exponential fits of the initial phase (peak force to inflection point) and late phase (from inflection point to full relaxation) of relaxation. AParvalbumin significantly different from AdlacZ (P < 0.05; one-way ANOVA and Student-Newman-Keuls multiple comparison test). BParvalbumin significantly different from vehicle (P < 0.05). Values are mean ± SE (n = 6–12). Time to peak twitch was not different between groups.