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Study in this Week's Issue of Cell Finds Injected Growth Factor Spurs Heart Regeneration
Date:7/23/2009

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When the team injected NRG1 into the peritoneal cavity of live mice after a heart attack, once daily for 12 weeks, heart regeneration was increased and pumping function (ejection fraction, assessed on echocardiograms) improved as compared with untreated controls. The NRG1-injected mice also lacked the left-ventricular dilation and cardiac hypertrophy that typify heart failure; both were seen in the controls.

When the researchers also stimulated production of a cellular receptor for NRG1, known as ErbB4, cardiomyocyte proliferation was further enhanced, demonstrating that NRG1 works by stimulating this receptor. They also identified the specific kinds of cardiomyocytes (mononucleated) that are most likely to respond to treatment.

In 2007, Kühn and colleagues first demonstrated that the heart has dormant regenerative capacities that can be reawakened. Kühn developed a sponge-like patch, soaked in a compound called periostin that is abundant in the developing fetal heart (and in injured skeletal muscle) but scarce in adult hearts. When the patch was placed over the site of cardiac injury in rats, it induced cardiomyocyte proliferation and improved heart function (Nature Medicine 2007; 13:962-9). Similar results were seen in larger animals, and periostin is now in preclinical development at Children's Hospital Boston for future application in human patients with heart failure.

The new work adds a second compound to the heart-regeneration toolbox, and reveals how both periostin and NRG-1 work at the cellular and molecular level, an essential step in predicting possible side effects. Both compounds ultimately act on the same cellular pathway, Kühn found.

"We applied periostin locally at the site of cardiac injury, but N
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