Timothy M. Olson, M.D.
Mutant gene causes deadly heart enlargement
Scientists have discovered how a defective gene can cause dilated cardiomyopathy, a condition that leads to heart failure, and suggest that blood pressure-lowering medications could benefit patients with this disease.
Timothy M. Olson, M.D., is one of the study’s two lead authors and is an assistant professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn. The study was supported in part by his American Heart Association National Center Clinician-Scientist Award.
In cardiomyopathy, weakened heart muscle causes the heart to enlarge and lose much of its pumping power. As a result, blood pools in the heart and backs up into the lungs, which causes congestive heart failure. Most cases of dilated cardiomyopathy are termed idiopathic, indicating that doctors have not been able to identify a cause of heart-muscle damage. The disease accounts for 10,000 deaths each year in the United States, Olson said.
In the early 1990s, a Mayo Clinic study revealed that at least 20 percent to 30 percent of dilated cardiomyopathy cases were familial, stemming from an inherited abnormal gene. “These findings were really a surprise, because it wasn’t thought at the time that genetics played such a significant role in the disease,” Olson said. “That study set in motion efforts to identify specific genes that are important in the development of dilated cardiomyopathy.”
By studying genetic material from 350 unrelated patients with dilated cardiomyopathy, Olson and his colleagues identified three mutations of a gene that makes a protein called metavinculin. Metavinculin is important in the process of heart muscle contraction. When the gene for metavinculin is mutated, heart muscle cells become more vulnerable to injury and the heart cannot contract and pump effectively.
While the only truly effective treatment for severe dilated cardiomyopathy is a heart transplant, some drugs can prolong patients’ lives. “Our findings suggest why reducing mechanical stress on the heart may be beneficial in patients with dilated cardiomyopathy,” Olson said. “One would predict that drugs that lower blood pressure and lessen the workload on the heart, such as beta-blockers and ACE inhibitors, would reduce mechanical injury to heart muscle cells and be beneficial to these patients.”
The study was conducted while Olson was on faculty at the University of Utah. He worked in concert with cell biologist Susanne Illenberger, Ph.D., of Technical University of Braunschweig, Germany.