Methylation of DNA is involved in its regulation and translation into RNA. This mechanism recently gained attention as a possible therapeutic target in heart failure. However, the role of DNA methylation of cardiomyocytes is controversial. Therefore, this study's authors investigated DNA methylation in cardiomyocytes under different conditions to better understand the disease as a prerequisite for new therapeutic approaches.
The scientists from the University Hospital in Hamburg (UKE), together with their colleagues in Singapore (Genome Institute of Singapore) and the United Kingdom (University of Nottingham) found important evidence that DNA methylation does indeed play a role. They investigated this by knocking out the most important form of the responsible enzyme, the DNA methyltransferase DNMT3A, in the heart using the CRISPR/Cas9 gene-editing technique in induced pluripotent stem cells. These cells were differentiated into cardiomyocytes from which the scientists then generated artificial heart tissue.
Numerous studies on this artificial heart tissue provided evidence that DNA methylation plays a role, especially under cell stress conditions, and seems to be particularly important for cardiomyocytes' lipid and sugar metabolism. The motor proteins of the cells, and thus their motility can also be influenced by DNA methylation.
The work of the international team led by Alexandra Madsen and Justus Stenzig from Experimental Pharmacology in Hamburg thus provides crucial new insights into the controversial debate about DNA methylation in cardiomyocytes. It provides hints in the search for new therapies for this common and serious disease.