© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy?
aLaboratory of Experimental Cardiology, University of Leuven, KUL, Campus Gasthuisberg O/N, 7th floor, Herestraat 49, B-3000 Leuven, Belgium
bDepartment of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands
cInterdisciplinary Research Center, University of Leuven, Kortrijk, Belgium
* Corresponding author. Tel.: +32-16-347-153; fax: +32-16-345844 karin.sipido{at}med.kuleuven.ac.be
Increased Na/Ca exchange (NCX) expression may be part of the genetic reprogramming in cardiac remodeling. In this review we address the following questions: (1) Is increased NCX activity a general feature of cardiac remodeling in hypertrophy and heart failure? (2) How does this contribute to the contractile and electrical phenotype of hypertrophy and heart failure? (3) Should be consider NCX a potential therapeutic target? From a review of the literature we found that NCX activity can be increased, unchanged, or even downregulated during cardiac remodeling. When NCX activity is increased, it can be considered compensatory for contractile function, but with negative side-effects, including an increased risk of arrhythmias. Changes in activity do not necessarily reflect changes in gene expression. Altered NCX acrtivity can also be consequent to changes in other Ca2+ fluxes or in [Na+]i homeostasis. The role of NCX in contractile alterations and arrhythmogenesis varies with the different stimuli or stages of cardiac remodeling. Pharmacological block of NCX in heart failure or hypertrophy may thus be useful, but most likely only in specific conditions, perhaps as part of a combined approach. Development of drugs that target only a specific mode of the exchanger may offer a further advantage.
KEYWORDS Arrhythmia (mechanisms); Hypertrophy; Heart failure; Na/Ca-exchanger
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