Triggering Tissue Regeneration in the Heart

A protein that can control cell function to repair damaged heart tissue could someday change the approach to treating heart disease, according to a new study.

Researchers at the University of Pennsylvania School of Medicine (Penn, Philadelphia, USA; www.upenn.edu) first identified the signals in the rat heart that currently prevent the ability to re-grow damaged heart tissue. The researchers then manipulated those signals so the heart could work to regenerate itself. Next, they investigated myocardial regeneration by initiating heart cell division and replication by expressing the cell-cycle regulator, a protein called cyclin A2. Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 or empty adeno-null.

Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. Using cyclin A2 expression via gene transfer yielded increased borderzone myofilament density and improved myocardial function. The cyclin A2 levels peaked at two weeks and tapered off by four weeks. These findings appeared in the July 4, 2006, issue of Circulation, the journal of the American Heart Association (AHA).

"We are examining the potential role of this regenerative strategy as a future therapy for heart failure,” said principal investigator Joseph Woo, M.D., of the division of cardiothoracic surgery at Penn. "Someday, this could lead to less surgery and perhaps even less medicine in treating heart disease.”

Cyclin A2 is unique in its control at two major transitions of the cell cycle and is the only cyclin that is completely silenced after birth in mice, rats, and humans.


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