An inherited form of dilated cardiomyopathy (DCM)—a rare heart disease that often causes sudden death or progressive heart failure—is caused by mutations in a gene called LMNA. Using stem cell techniques to grow human heart muscle cells containing mutations in LMNA, researchers found that these mutations severely disrupt the structural organization of DNA in the nucleus of heart muscle cells. This, in turn, lead to the abnormal activation of non-heart muscle genes.
The researchers also found similar abnormalities in gene activity when they examined cells taken from people with DCM who had LMNA mutations. These heart muscle cells containing mutated LMNA also lost the mechanical elasticity that normally allows them to contract and stretch as needed. The same deficiency was not seen in liver and fat cells with a mutated LMNA gene.
Research is ongoing to understand the changes in elasticity in the heart cells with LMNA mutations. The study, published in the journal Cell Stem Cell, was partly-funded by NHLBI.