Protein in cardiac muscle cells may play a crucial role in heart failure prevention

Jan 5 2005

Scientists at the University of North Carolina at Chapel Hill School of Medicine have shown that a protein in cardiac muscle cells may play a crucial role in heart failure prevention.

The protein is known technically by the unusual acronym MuRF1, or muscle-specific RING finger 1, and helps regulate cardiac cellular molecules involved in abnormal enlargement of the heart. This condition, known medically as cardiac hypertrophy, occurs in 50 percent to 60 percent of people older than age 70 and makes them more prone to developing a potentially fatal type of heart failure.

"People who develop cardiac hypertrophy are prone to diastolic heart failure. Their hearts contract normally but the thickened heart muscle can't keep the blood out of the lungs," said Dr. Cam Patterson, the study's senior author. Patterson is Henry A. Foscue distinguished professor of medicine and cardiology, and professor of pharmacology and cell and developmental biology at UNC. He also directs the Carolina Cardiovascular Biology Center.

In a report published in the Proceedings of the National Academy of Sciences on Dec. 28, Patterson and co-authors said MuRF1 was responsible for signaling other molecules in heart cells to degrade another protein called troponin-1, a key player in heart muscle activity.

"Troponin-1 is a critical component of the cardiac contractile machinery," Patterson said. "It's part of the cardiac muscle cell that makes heart muscle beat."

When heart cells hypertrophy, or become enlarged, troponin-1 and other contractile proteins greatly increase in abundance, Patterson said. "And so one of the critical ways that MuRF1 reverses hypertrophy is by degrading proteins such as troponin-1."

Thus, the action of MuRF1 appears to determine the balance between hypertrophic (enlargement) and anti-hypertrophic signals in heart muscle cells, Patterson added. "This is really a fundamental observation. It has been known for some time that contractile proteins are degraded, but the specific molecules involved have not been defined until now."

Cardiologists consider cardiac hypertrophy as one of the most potent predictors for adverse cardiac outcomes, such as heart failure and arrhythmias, or abnormal heart rhythms. "It's as bad to have cardiac hypertrophy as it is to have had a heart attack," said Patterson. "Unfortunately, we have no specific therapies aimed at this condition. But our findings suggest that new drugs might be developed to reverse hypertrophy by targeting these ubiquitin ligase signaling pathways in cardiac cells."