March 2004
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Journal of Clinical Investigation
Gene therapy for a broken heartDespite significant advances in the treatment of cardiac disease, chronic heart failure remains a leading cause of morbidity and mortality. Gene therapy represents a potential new strategy for the treatment of cardiac dysfunction. In the March 1 issue of the Journal of Clinical Investigation John Ross, Jr., and colleagues from the University of California, San Diego, report that gene delivery to express a modified form of the phospholamban protein, S16EPLN, to chronically failing rat hearts after a heart attack exerted many beneficial effects. The report suggests that S16EPLN gene delivery shows promise as a novel strategy for the treatment of chronic heart failure.
The presence of S16EPLN upregulated the activity of the enzyme SERCA2 in transduced cells and compensated for defects in calcium uptake during heart failure. Echocardiographic and hemodynamic measurements showed improvements in global heart function and contractility in rats that received S16EPLN treatment. In addition, the formation of scar tissue was suppressed in these animals. Although further long-term studies are necessary to clarify the effects of modifying phospholamban on arrhythmias, gene transfer of S16EPLN shows promise as a novel therapeutic strategy.
TITLE: Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats
AUTHOR CONTACT:
John Ross Jr.
University of California, San Diego, La Jolla, California, USA.
Phone: 858-822-2267
Fax: 858-534-1626
E-mail: [email protected]
View the PDF of this article at: http://www.jci.org/cgi/content/full/113/5/727
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