Protein switch could aid recovery after heart attack

Fibroblasts (red) expressing endothelial markers (green)--Courtesy of Eric Ubil/UNC

By switching on a protein in the heart, scientists may be able to improve recovery in patients that have just endured a heart attack.

Investigators at the University of North Carolina (UNC) School of Medicine found that when a protein called p53 was turned on--or overexpressed--in mice, this seemed to be connected to the healing process of endothelial cells, which help rebuild blood vessels to supply oxygen and nutrients to the heart after cardiac injury.

Detailed in the journal Nature, researchers induced heart attacks in mice and then studied cells called fibroblasts, which normally give rise to scar tissue after a heart attack, to see if the cells expressed markers characteristic of endothelial cells. Almost a third of the fibroblasts in the area of the cardiac injury expressed these endothelial markers, and the fibroblasts that developed into endothelial cells eventually gave rise to functioning blood vessels.

The UNC researchers showed that an overexpression of p53 in the fibroblasts after heart injury seemed to control whether fibroblasts became endothelial cells.

When investigators knocked out the p53 gene in scar-forming cells in adult mice, it decreased the number of endothelial cells by 50%. The researchers then tested the opposite--mice were treated with a drug that would increase the level of p53 for a few days after experiencing a heart attack. The experimental drug, called RITA--reactivation of p53 and induction of tumor cell apoptosis--doubled the number of fibroblasts that turned into endothelial cells, from 30% of fibroblasts naturally switching into endothelial cells to 60%.

There are no approved drugs to help prevent or regenerate scar tissue following a heart attack, but GlaxoSmithKline ($GSK) is currently studying its drug darapladib, meant to prevent subsequent heart attacks in people that have already had an attack, in Phase III clinical trials.

- get more from the UNC
- see the study abstract