Atherosclerotic vascular disease remains the primary cause of mortality and morbidity. DZHK investigators at the Rhine-Main partner site (Frankfurt) have identified a novel RNA-based mechanism that regulates pro-inflammatory gene expression in atherosclerotic heart disease. Their findings have been published in the Nature Medicine.
The international research team led by Konstantinos Stellos and Stefanie Dimmeler from the Institute of Cardiovascular Regeneration and Department of Cardiology at Goethe University Frankfurt provided several lines of evidence for an important role of RNA modifications in the regulation of gene expression and endothelial cell function. By using RNA-sequencing and advanced molecular biology techniques, they showed that adenosine deamination in RNA level by ADAR1, a process called adenosine-to-inosine RNA editing, of the extracellular matrix degradation enzyme cathepsin S, an enzyme with a well-established role in the development and prognosis of cardiovascular and tumor disease, alters the RNA-protein interaction controlling cathepsin S mRNA stability and expression in inflammatory vascular diseases.
Taken together, this study reveals a previously unrecognized role of RNA editing in human atherosclerosis.