Blocking Molecular 'Cross-Talk' May Prevent Heart Failure

Surgeons at the University of Cincinnati College of Medicine have received $1.5 million to study “signaling pathways” that may cause heart enlargement (hypertrophy) to progress to heart failure. 

Heart failure is a condition in which the heart muscle becomes very weak. It is most often the result of multiple genetic disorders and coronary artery disease, in which plaque builds up inside the arteries, reducing blood flow and “starving” the heart muscle. As a result, the heart is unable to pump enough oxygen and nutrients to vital organs throughout the body.

According to the American Heart Association, heart failure is the leading cause of hospitalization in adults over 65, and more than 5 million people in the United States suffer from the disease.

Shahab Akhter, MD, a cardiac surgeon and principal investigator for the study, believes that protein kinase C—a molecule that is activated when the heart becomes enlarged—“turns on” a specific enzyme that limits the heart’s ability to respond to stress and pump efficiently. This can lead to poor heart function and, ultimately, heart failure.

Dr. Akhter and his team will study the interaction between these two signaling molecules in multiple lines of genetically engineered mice—each designed to express a specific kinase or kinase inhibitor—in order to identify new ways to prevent heart function deterioration.

“If we can identify and block this molecular ‘cross-talk’ that contributes to heart failure, we can develop new, more precise therapies that reduce the incidence of disease and save more lives,” Dr. Akhter says.

Heart disease is currently treated with a combination of drugs that reduce stress on the heart and improve blood flow. These include ACE (angiotensin-converting enzyme) inhibitors, which reduce blood pressure; beta-blockers, which block receptors to slow the heartbeat and reduce muscle contractions; and diuretics, which help the body remove unneeded water and salt. 

“Beta-blockers and ACE inhibitors are effective in treating the symptoms of heart failure, but clearly we need to do better. The average survival rate for someone with heart failure is just five years,” says Dr. Akhter.

The five-year, basic science study is funded by the National Institutes of Health, National Heart, Lung and Blood Institute and Thoracic Surgery Foundation for Research and Education.