Scientists are unraveling the molecular mechanisms behind dilated cardiomyopathy (DCM), the most common inherited disease of the heart muscle. From the University of Toronto in recent Proceedings of the National Academy of Sciences
paper, researchers completed a first-of-its-kind study that could help explain causation behind many heart diseases.
Researchers analyzed muscle tissue from mice models of DCM as soon as they started to see enlargement of the heart, the key sign of the disease. A heart that is too big cannot pump blood at the right rhythm, which can lead to heart failure. While scientists are aware of many genetic associations with the development of the disease, there’s a lot that they don’t understand completely as to why people have DCM.
Specifically, the study involved mapping changes in protein signaling pathways in mouse heart cells genetically predisposed to develop DCM as compared to normal mouse heart cells. Researchers introduced a mutation similar to the one that is associated with DCM in humans to design one set of mice models to be destined for DCM. They scanned patterns of protein phosphorylation to look for differences between DCM and healthy mice, a molecular process that regulates the activity of protein signaling networks.
After collecting heart samples from both the control mice and experimental mice, they compared proteins collected from a time when the heart muscle was just starting to stretch, and they ended up discovering hundreds of signaling pathways that “went off course” in the DCM mouse hearts, making it the first comprehensive map of molecular signaling events.
"We expect to be able to detect specific changes in signalling pathways in different cardiac patients," said Toronto’s Dr. Uros Kuzmanov. "And our approach is not limited to the DCM; it could be applied to all heart disease."
Next, the group plans on conducting a similar experiment using human tissue, with their long term goal being to potentially help scientists and practitioners identify new drugs targets and biomarkers to detect DCM better and earlier.
Sources: University of Toronto
, American Heart Association