Modified Protein May Reduce Heart Attack Damage

Scientists modified a protein in the heart that greatly reduced cell damage after heart attacks, according to new research. The modified protein reduced cell damage by 50% in mice without causing damaging inflammation. These findings came during research looking at ways to prevent heart failure induced by heart attacks.

The study’s findings were published ahead of print March 1, 2012, in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology. The protein is called focal adhesion kinase (FAK). It organizes cell structure by triggering various processes that help the cells stay alive. “FAK is important for basic processes in all cells, and it appears to be important for cell survival, growth and migration in a number of cell types, but is especially critical in the heart,” said Joan Taylor, PhD, who has been studying FAK in mice at the department of pathology and lab medicine at the University of North Carolina (UNC; Chapel Hill, USA).

FAK can also create problems. In an earlier research snag, the scientists discovered that it was activated in the heart after a heart attack, and triggered a series of events that could lead to inflammation and permanent heart damage. “Inflammation is important to get rid of dead cells, but if that goes uncontrolled, the inflammation kills viable heart cells,” Dr. Taylor said.

That is when the researchers began working to construct a better FAK, one that would initiate the survival response without causing excessive inflammation. Dr. Taylor’s former UNC colleague, Mike Schaller, PhD, created what they called SuperFAK, which exhibited increased but controlled activity.

In mice with the new SuperFAK gene, researchers saw a massive activation of FAK after heart attack, and not as many heart cells died compared to unmodified mice. Three days after the induced heart attack, the SuperFAK mice had approximately 50% less heart injury than the unaltered mice. This benefit was maintained for eight weeks. “We think because the modified FAK resolved its activity in 24 hours, it limited the inflammation response, and only activated beneficial signals,” Dr. Taylor said.

FAK also plays a role in the development of a number of cancers and it has been associated with tumor growth and metastases. Some chemotherapy agents hinder FAK, leaving the heart susceptible to damage. Progressive cardiac damage is a typical adverse effect of several chemotherapeutic treatments. In the future, the investigators hope to develop drugs to target FAK to protect the heart during chemotherapy or following a heart attack.

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