In vivo acceleration of heart relaxation performance by parvalbumin gene delivery
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
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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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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In vivo hemodynamics by catheter-based micromanometry. (a) Pressure (top...
In vivo hemodynamics by catheter-based micromanometry. (a) Pressure (top traces) and first derivative of pressure (dP/dt; bottom traces) recordings at day 6 after vehicle or AdlacZ or Adα-PV gene transfer. (b) Summary of hemodynamic data. HR, heart rate; Pmax, peak pressure; dP/dtmax, maximum positive dP/dt; dP/dtmin, maximum negative dP/dt; 1/2 RT, time from peak pressure to one-half decay in pressure; RT90, time from peak pressure to 90% decay in pressure. Values are mean SEM (n = 9–10). AAdα-PV significantly different from vehicle and AdlacZ (P < 0.01 for Pmax data and P < 0.05 for dP/dtmin data). BAdα-PV significantly different from AdlacZ, P < 0.01. CAdα-PV significantly different from vehicle, P < 0.05.