Researchers Explore First Treatment for Common Form of Heart Failure

The heart adapts to many types of chronic stress by undergoing hypertrophy, a thickening of the heart muscle. In the presence of diseases such as hypertension and heart valve disorders, cardiac hypertrophy is a very common and dangerous condition that can lead to heart failure and even death. The process of hypertrophy involves not only an increase in muscle mass, but also changes in the properties of the muscle that lead to heart failure, along with fibrosis, inflammation and loss of blood supply.

Nanette H. Bishopric, M.D.

There is currently no treatment for hypertrophy, but researchers at the University of Miami Miller School of Medicine are conducting studies that may lead to the first. An article detailing their findings, “Reversal of pathological cardiac hypertrophy via the MEF2-coregulator interface,” was published online September 7 by the journal JCI Insight. Nanette H. Bishopric, M.D., professor of medicine, and Jianqin Wei, M.D., assistant research professor of medicine, coauthored the article with the assistance of their research team.

The researchers have shown that hypertrophy develops when stress causes two key proteins to interact in the cell nucleus, profoundly altering the expression of many genes. They also found that a new compound, designed to prevent these two proteins from interacting with each other, can prevent and reverse pathological hypertrophy and improve heart function — even when the stress is ongoing.

“It has long been debated whether or not cardiac hypertrophy is a good or a bad response to stress,” said Bishopric. “Our results show that hypertrophy is not only unnecessary for adapting to stress, but also is actually harmful, and that reversal of hypertrophy restores heart function. Our approach shows that we may be able to treat many forms of heart failure — especially the kind associated with preserved ejection fraction — by targeting the cardiac myocyte stress response.”

The next step, the researchers say, will be studies in larger animals, as well as more detailed assessment of toxicity, pharmacokinetics and side effects, and further confirmation of the mechanism of action.

Funding for the study was provided by NIH’s National Heart, Lung and Blood Institute, and by the Miami Heart Research Institute.

Tags: cardiac hypertrophy, heart failure, JCI Insight, Jianqin Wei, Miller School of Medicine, Nanette H. Bishopric, University of Miami