Lub-dub. Your heart beats, pumping blood through your body. Lub-dub. First stop: your coronary arteries, which will give blood to your heart muscle itself so it can continue to work. Lub-dub. But this time, something is blocking one of your coronary arteries. A section of your heart receives no blood. Lub-dub. Another heartbeat, no blood again. No blood. No oxygen. No nutrients. Your heart-muscle cells keep beating, exhausting their stores. Lub-dub. The starved cells tire, and finally, they begin to die. These cells, called cardiomyocytes, don’t reproduce—when they die, your body does not replace them. Lub-dub. Another heartbeat and the blockage loosens. Blood flows through the artery again; oxygen returns to your starved cells. But paradoxically, the newly oxygenated blood can be detrimental to your cardiomyocytes and lead to further destruction.

Cardiomyocytes are amazing little powerhouses. They have a resistance to fatigue stress and disease that other cells can’t match. Your cardiomyocytes are with you for your entire lifetime, and can beat upwards of two and a half billion times. But in some situations, such as heart attacks, the cells’ resistance is stretched to its limit. Pathologist Joan Taylor wanted to know if she could manipulate cardiomyocytes to help them survive under extreme conditions.

In cardiomyocytes, an important protein for survival is focal adhesion kinase, or FAK. Once activated, or turned on, FAK can send messages throughout the cell. “FAK is thought to send the signals to the cells to divide or migrate or survive,” Taylor says.

Studies conducted by Taylor and others as early as 1995 revealed that mice genetically modified to eliminate FAK don’t produce offspring. Their embryos can’t fully develop. “Death occurs at about the time when the cardiovascular system is developing,” Taylor says. “And there are major impairments in the heart and the blood vessels.” In later studies, when mice were modified to remove FAK after birth, their hearts seemed to function normally.

That is, until diseases came into play. Zhaokang Cheng, who worked on Taylor’s current study, found that when cardiomyocytes were exposed to stress, cells that had no FAK were prone to self-inflicted death—a kind of cell suicide known as apoptosis. Taylor’s group reasoned that adult hearts depleted of FAK might be worse off following a heart attack.

When her group examined these cells in mice following a simulated heart attack, they found that Taylor was right: the cells were more likely to die. “So,” Taylor says, “the question then was: can we provide some survival benefit by activating FAK in the heart?”

Simply increasing the amount of FAK in the heart or keeping it constantly activated didn’t seem like the answer. Past experiments by groups studying other survival proteins had shown that this method does more harm than good. And studies by cancer biologists throughout the 1990s determined that FAK plays an important role in the survival of cancer cells; more FAK might lead to dangerous side effects. But then a protein chemist named Mike Schaller found a part of FAK that, when carefully modified, could increase the protein’s activation at only the specific times when it’s needed.

Taylor and her colleges introduced the modified version of FAK, called SuperFAK, into mice before delicate surgery performed to mimic a heart attack. Following this surgery, Cheng compared the damage that occurred in the hearts of normal mice with those expressing SuperFAK. Mice with SuperFAK showed an increase in active FAK levels in the heart. This not only decreased cell death, but greatly improved the heart function in SuperFAK mice for eight weeks after injury.

“At different time points we measured heart function and found that it was much better in SuperFAK mice,” Cheng says. “We also measured the cardiomyocyte apoptosis and found it was significantly decreased in these mice.”

The protective value of FAK in the heart was clear. And enhancing FAK activity could dramatically increase a cell’s chance of surviving a heart attack. But we can’t genetically modify humans to express SuperFAK just in case they have a heart attack some day. So what benefit does this information provide? It’s a starting point. “Potentially, the best way to go would be to see if we could find drugs that would mimic this,” Taylor says.

Administering such drugs during or immediately following a heart attack could reduce the long-term damage to the heart. And they could have other roles in protecting the heart from damage under different circumstances. “Chemotherapy can induce cardiomyopathy,” says Cheng, “so there is potential for other protective value to the heart.”

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Sarah Creed is a postdoctoral research associate in James Bear’s lab in the UNC Lineberger Comprehensive Cancer Center.

Joan Taylor is an associate professor in the Department of Pathology and Laboratory Medicine in the UNC School of Medicine. Zhaokang Cheng is a postdoctoral associate in her laboratory. The paper, “Targeted focal adhesion kinase activation in cardiomyocytes protects the heart from ischemia/reperfusion injury,” was published in the April 2012 issue of Atherosclerosis, Thrombosis and Vascular Biology.