Discovered a mechanism for preventing heart tissue to repair itself

Fabric of the heart muscle is actually not able to recover. Why cardiovascular disease is so dangerous — in many countries (including, in the United States and Russia) they are the most common cause of death for both men and women. Scientists from the Medical College of Baylor (Baylor College of Medicine) and Texas heart Institute (Texas Heart Institute), inspired by the idea of self-healing of the heart, decided to study the signaling pathways used by the cells of the heart tissue. The researchers were able to detect a previously unknown link between the processes that prevent the heart to recover. The results, published in the journal Nature, may in the future lead to strategies that will make the update of cardiac tissue possible.

“We look at why the cardiac muscle is not updated, says the study’s lead author, Dr. James Martin (James Martin), Professor of regenerative medicine from the Medical College of Baylor. In the new study we focused on two signaling pathways used by the cardiomyocytes, the muscle cells of the heart. We studied the Hippo signaling pathway, which stops the update of Mature cardiomyocytes, and signal the path of the dystrophin-associated glycoprotein complex (DAG-complex), essential for normal functioning of these cells.”

The signal path is a sequence of molecules through which information from the cell receptor is transmitted inside the cell. The signal is transmitted from molecule to molecule in a very specific manner that allows us to speak about signaling pathways. Most signaling pathways are activated in response to external to the cell signals such as neurotransmitters, hormones and growth factors. The minority also begins with signals generated inside the cell.
Scientists also studied the mutation of genes associated with the synthesis of the DAG complex, because people with such mutations develop dangerous genetic disease, muscular dystrophy or, as they are called, muscular dystrophy.

In previous works it was shown that the components of the signaling pathway of DAG complex can somehow interact with components of the Hippo signaling complex. In the new study, Dr. Martin and his colleagues studied the effects of these interactions in animal models. With the help of genetic engineering the researchers deduced mice that lacked genes associated with first, second, or both signal paths. The researchers then observed the condition of the heart tissue of animals and its capacity for renewal. The study was first shown to dystroglycan-1, a component of the signaling pathway of DAG-complex directly attached to the protein Yap, a component of the Hippo signaling pathway. It is this attachment and blocks the process of dividing cardiomyocytes.

“The discovery of the fact that Hippo signaling pathway and DOUG intersect at the cells of the heart and act as a “brake” cell division, opens new perspectives. Maybe someday the destruction of this interaction of signaling pathways will lead to the fact that we “teach” Mature cardiomyocytes to proliferate, for example, to heal the damage caused by myocardial infarction,” says Dr. Martin.

Also a new study can be used to improve heart function in children suffering from myodystrophy.

“Patients with muscular dystrophy often suffer from serious cardiac disorders, explains Dr. Martin. Our findings may help in developing medicines that slow progression of these disorders by stimulating the proliferation of cardiomyocytes. But to achieve this, it is necessary to conduct additional studies of signaling pathways that control the growth of heart cells.”