A sometimes fatal enlargement of the heart can be inherited or acquired through an infection. In this month's issue of Nature Medicine, scientists show that the virus causes the symptoms in much the same way as faulty genes do, suggesting that a single therapy could work against the disease.
Dilated cardiomyopathy, which can cause shortness of breath and result in heart failure and death, affects about 50,000 people in the United States each year. For several years, researchers have known that as many as a third of patients suffer from viral infections, most of them with the Coxsackie B virus. The infections swell and irritate the heart, sometimes resulting in chronic inflammation that can lead to cardiomyopathy. But cardiomyopathy can also be brought on by genetic disorders like muscular dystrophy, which causes abnormalities in a protein called dystrophin. Dystrophin is responsible for linking the cell membrane to contractile proteins such as actin and allows the contraction force inside cells to be transmitted to the outside.
Cardiologist Kirk Knowlton of the University of San Diego and his colleagues wanted to find out whether the Coxsackie B virus also affected dystrophin. The researchers showed that in test tubes, proteins produced by the Coxsackie B virus broke apart dystrophin but not other proteins found inside heart cells. After cultured rat heart cells were infected with the Coxsackie B virus, the amount of normal dystrophin declined within 3 days. Finally, the researchers injected immune-deficient mice with the Coxsackie B virus. When they killed the animals a week later, they found that the virus had broken apart dystrophin in their hearts and that the membranes of heart cells infected with Coxsackie B virus were more permeable to blue dye than uninfected cells. This implies that the dystrophin breakdown damaged the cell membranes, says Knowlton; this weakening of cell membranes allows the virus to spread, but damages the heart, because it makes the cells less resilient and less able to contract efficiently. In an attempt to keep pumping enough blood, the heart starts becoming bigger.
The study is the first to show that damaged dystrophin underlies both genetic and acquired cardiomyopathy, says Jeffrey A. Towbin, a cardiologist with the Baylor College of Medicine and Texas Children's Hospital in Houston. This similarity suggests that researchers should target the underlying process in the different varieties of the disease, he says, for example by developing a drug to prevent dystrophin from breaking down.