Heart failure is a major cause of mortality but there has been no therapy specifically targeted at the underlying cellular mechanisms leading to chronic myocardial dysfunction. In 22 July advanced online Nature Medicine Masahiko Hoshijima and colleagues from University of California, San Diego, show that transcoronary gene transfer of phospholamban (PLN) — a key regulator of cardiac sarcoplasmic reticulum — is a potential therapy for progressive dilated cardiomyopathy and associated heart failure (Nat Med 2002, DOI:10.1038/nm739).

Hoshijima et al. used an in vivo recombinant adeno-associated virus (rAAV) transcoronary delivery system to express a pseudophosphorylated mutant of human PLN in cardiomyopathic hamsters. They observed that the rAAV/S16EPLN treatment enhanced myocardial sarcoplasmic reticulum Ca2+ uptake and protected cardiac myocytes from cytopathic plasma membrane disruption. In addition, rAAV/S16EPLN treatment prevented low left ventricular (LV) systolic pressure and deterioration in LV relaxation.

"Given that there is currently no therapy for...

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