The role of Dhx36 in cardiomyocyte differentiation redefines the clinical approach to the treatment of arrhythmias.

An international team of researchers has identified a protein that is critical for the development and functioning of the cardiac conduction system. This discovery represents significant progress in understanding the mechanisms that regulate heart function and opens up new opportunities for research into the treatment of heart disease. The study, led by the Supreme Scientific Research Council (CSIC) and published in the journal Nature Communications, reveals the important role of the Dhx36 protein in regulating cardiomyocyte differentiation and the proper development of the cardiac conduction system.

The discovery of the role of the Dhx36 protein in the cardiac conduction system represents an important advance in cardiac biology. This research not only provides key information about the molecular mechanisms that regulate heart function, but also suggests new ways to treat heart diseases that affect the transmission of electrical impulses.. As research on this protein advances, new therapeutic approaches may be developed to improve heart health in patients with heart failure and other pathologies related to conduction system function.

Protein Dhx36

The study, which used animal models, was carried out by scientists from the Center for Molecular Biology of Severo Ochoa (CBMSO-CSIC), the Research Institute of Rare Diseases of the Carlos III Health Institute (ISCIII), the National Center for Cardiovascular Research (CNIC). , Universidad Pompeu Fabra (UPF) and other research centers in Spain. The group was led by Pablo Gómez del Arco (ISCIII), Pura Muñoz-Cánoves (Pompeu Fabra University and Altos Laboratories) and Juan Miguel Redondo (CBMSO).

The main finding of this study is the identification of the Dhx36 protein as a key regulator of the differentiation of cardiomyocytes, cells specialized in contraction of the heart muscle.. As explained Pablo Gomez del Arco, ISCIII scientist“The Dhx36 protein modulates gene networks that control cardiomyocyte differentiation by resolving G-quadruplex structures in the promoters of key cardiac conduction system genes.” This process is necessary for the proper formation of conduction system cells responsible for transmitting and controlling the electrical impulses of the heart.

The conduction system of the heart includes a network of specialized fibers that provide synchronization of heartbeats, which is critical to maintaining an adequate heart rate. The study shows that mice in which the Dhx36 protein was removed from cardiomyocytes developed serious heart problems, such as dilated cardiomyopathy and a blockage in the transmission of electrical impulses between the chambers of the heart, especially between the atria and ventricles.. According to Pura Muñoz-Cánoves, scientist at Pompeu Fabra University and Altos Labs “Removal of Dhx36 during embryonic development dramatically affects cardiac health, leading to profound functional changes of the heart.”

Future prospects

The study not only provides a better understanding of the development of the cardiac conduction system, but also provides valuable information about heart disease in humans. Mice lacking Dhx36 developed dilated cardiomyopathy, a condition in which the chambers of the heart become enlarged and cannot pump blood effectively.. Additionally, in adult cardiomyocytes, lack of Dhx36 resulted in the formation of left atrium blood clots, suggesting that this protein is critical for postnatal heart health.

Juan Miguel Redondo (CBMSO), another of the study leaders, emphasizes the relevance of these results for clinical medicine: “Defects in Dhx36 may be associated with certain heart diseases and have important clinical consequences, such as affecting the electrical activity of the heart and the development of forms of dilated cardiomyopathy.” This opens up new opportunities for research into treatments aimed at improving the conduction system of the heart and preventing heart failure resulting from changes in the function of this protein.

Molecular mechanisms

One of the main points of the study isconnection between the Dhx36 protein and G-quadruplex structurespresent in both DNA and RNA. These structures, if not properly resolved, interfere with the transcription of key genes that regulate cardiac function. In the absence of Dhx36, these structures accumulate in cardiomyocyte genes, causing a block in the expression of genes required for heart development.

This finding suggests that Dhx36 may be a therapeutic target for the treatment of cardiac conduction system diseases.

If we can interfere with the activity of this protein or the G-quadruplex structures, it may be possible to develop treatments that improve the electrical functioning of the heart in patients with diseases such as dilated cardiomyopathy.

Scientific cooperation

The success of this research is largely due to the collaboration of various scientific institutions in Spain. Research groups from the Health Research Institute of the San Carlos Clinical Hospital, led by José Luis de la Pompa and David Filgueras, also made significant contributions to the development of the project. This study was funded by the Ministry of Science and Innovation through the Government Research Agency, CSIC, Pro CNIC Foundation, La Marato Foundation and CIBER Cardiovascular Diseases (CIBERCV) ISCIII.

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