Overexpression of NCX1 does not by itself lead to contraction abnormalities in the heart

Nov 23 2009

Researchers from the Center for Translational Medicine at Thomas Jefferson University have found that the overexpression of a sodium/calcium exchanger, without changes in other ion transport pathways commonly observed in heart failure, does not by itself lead to contraction abnormalities in the heart. They presented the data from the study at the American Heart Association Scientific Sessions in Orlando, Fla.

Led by Joseph Cheung, M.D., Ph.D., Capizzi Professor of Medicine and director of the division of Nephrology at Jefferson Medical College of Thomas Jefferson University, the research team engineered a novel mouse model in which the expression of the sodium/calcium exchanger protein (NCX1) could be turned on and off, by withholding doxycycline from the mouse feed.

NCX1 normally removes calcium from the heart. Under some conditions, NCX1 can also add calcium to the heart. According to Dr. Cheung, calcium controls the strength of the heartbeat. If there is too little calcium, the heart will beat less strongly. But if there is too much, it may cause irregular heartbeat, also known as arrhythmias. Depending on the stage of heart failure, the expression of NCX1 is changed.

In some models of heart failure, as well as some stages of human heart failure, NCX1 expression is increased and thus hypothesized to contribute to contractile dysfunction, according to Dr. Cheung. But it is still unknown whether NCX1 expression on its own leads to heart failure. It is also controversial whether NCX1 overexpression is beneficial or detrimental in heart failure.

"Based on the results of our study, it appears as though overexpression of NCX1 in heart failure states, must interact with other proteins and genes to have a negative influence on the heart," Dr. Cheung said. "But its overexpression alone does not appear to cause heart failure in our model."

Dr. Cheung will now use their novel mouse model to test the overexpression of NCX1 in mice that have conditions like hypertension or low blood flow states, to determine if it is it is protective of the heart. Depending on these future studies, gene therapy to stimulate the overexpression of NCX1 could be a possible therapeutic target for these patients.

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