It’s What’s on the Outside that Counts

When we think about disease, we often wonder what has changed insideaffected cells. Yet, perhaps taking a look at the surrounding environment is just as important. In the case of hypertrophic cardiomyopathy (HCM), a disease marked by thickening of the heart muscle, changes in the environment around the cell, or the extracellular matrix, can be detrimental to the normal functioning of the heart. Currently, HCM treatments focus on curbing symptoms, rather than reversing the damages in the heart. 

A research team led by Yale professor of Biomedical Engineering Stuart Campbell recently investigated the effects of extracellular environment on heart muscle functions. After thin slices of healthy heart muscle cells were taken from a swine model and purified, they were inserted into one of two environments—either a healthy or diseased extracellular matrix. Surprisingly, the two showed dramatically different behavior. “Once we grew the cells on the diseased and normal extracellular matrices, we saw that the cells on the diseased matrix took on characteristics that were indicative of disease,” said Lorenzo Sewanan, the lead author of the study. While the heart muscle cells grown on the healthy extracellular matrix behaved healthily, the ones grown in the diseased environment exhibited symptoms of HCM. “We saw that these engineered heart tissues were hypercontractile—they contracted harder and slower,” Sewanan remarked.

According to Sewanan, the results offer exciting new possibilities to improve existing treatment options for HCM. “With drugs that have been developed already, you can stop HCM from getting worse, but you can’t reverse it,” Sewanan said. “Once significant structural remodeling has occurred, you might stop the disease and attenuate some of the symptoms, but you can’t reverse it because the drug is treating the disease inside the cells, not outside them”. Currently, drug therapy creates the same situation Sewanan studied—normal cells in a diseased environment. Although the cells are normal, they cannot function properly, as the damage to the extracellular matrix has already been done. Perhaps, it’s what’s on the outside that counts when considering treatment of HCM.