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New clues to heart muscle thickening

Medicine@Yale, 2019 - November December


Hypertrophic cardiomyopathy (HCM), in which the heart muscle grows too thick and contracts too hard, is often caused by mutations in the cardiac form of the muscle protein myosin. But Stuart Campbell, PhD, associate professor of biomedical engineering and of cellular and molecular physiology, suspected that changes to the extracellular matrix (ECM), the scaffolding that supports cells, might contribute to HCM.

To test that hypothesis, Campbell and his team took diseased heart muscle from pigs that serve as animal models of HCM, chemically removed the cells, and seeded the decellularized and diseased matrix—as well as a control matrix from healthy pigs—with healthy human heart cells generated in cell culture.

As Campbell and his team reported July 24 in JACC: Basic to Translational Science, the diseased matrix was stiffer than its healthy counterpart, and the tissue that resulted from the seeding of healthy cells onto diseased matrix exhibited the contractile defects of HCM.

The stiff diseased matrix may have triggered the hypercontractility in the healthy heart cells, the authors suggest. Future work will investigate how the ECM affects contractility, Campbell says.