Helping hearts

Little did Daria Mochly-Rosen, PhD, know that the enzymes she was studying purely to learn how they work would lead to discoveries that could help people with heart disease.

Minnie Sarwal, MD Mochly-Rosen, professor of chemical and systems biology, is now using two grants from the American Recovery and Reinvestment Act to develop strategies to protect hearts from injury. But the work can be traced back more than 20 years when she was looking for a way to test her theory about how members of a particular family of enzymes are turned on.

A colleague suggested she study heart attack, a condition in which these protein kinase C enzymes are activated. She proved her theory — radical at the time — that PKCs get turned on by linking with certain proteins on cell membranes.

In the process, she also found that activating one particular member of the PKC family — epsilon PKC — helped laboratory animals weather the repercussions of heart attack. She also found another role for the enzyme. Researchers had observed that moderate alcohol consumption had a similar protective effect and knew that the effect was helped along by a member of the PKC family, but they didn’t know which member. Mochly-Rosen discovered it was epsilon PKC as well.

Since then, Mochly-Rosen has identified drugs that mimic this alcohol-induced protective effect. She’ll use a $231,000 stimulus grant to learn more about how epsilon PKC controls another protective enzyme: ALDH2, which is mutated in 50 percent of East Asians. The stimulus package allowed the hiring of a medicinal chemist, who will further develop drugs to activate normal and mutant ALDH2 to help hearts starved of a healthy blood supply.

A second grant, for $293,000, will allow Mochly-Rosen to continue studies of epsilon PKC and a related enzyme called delta PKC, which acts as yin to epsilon PKC’s yang. While activation of epsilon PKC leads to cardiac protection, activation of delta PKC leads to heart damage. To learn how the cell removes debris that accumulates by heart attack, she hired an experienced cell biologist; proper removal of the debris is essential for normal heart function.

Mochly-Rosen hopes that these two studies will identify drugs to treat injuries associated with heart attack. It’s a big deal, since no treatments yet exist.