Extracellular Ribonucleic Acids (RNA) Enter the Stage in Cardiovascular Disease

Inflammatory and ischemic cardiovascular diseases, especially atherosclerosis and myocardial infarction, remain the number one cause of death in the Western world, whereas the therapeutic options currently available are still limited. Several recent findings have indicated that nucleic acids, particularly extracellular ribosomal RNA and micro-RNAs, significantly contribute to the adverse outcome of atherosclerosis, myocardial infarction, and other cardiovascular diseases. Extracellular RNAs act as novel danger-associated molecular pattern signals and potent cofactors in cardiovascular inflammation and thrombosis, particularly when accumulating in the extracellular space under tissue-damaging or pathological conditions. In this concise review article, the different entities of extracellular RNAs, their cellular sources, and their putative functional contribution to the pathogenesis of cardiovascular diseases will be discussed. In fact, it remains a tightrope walk for these polyanionic molecules outside cells to promote defense reactions on the one side but to provoke cardiovascular disease development on the other side, dependent on their concentration, the environmental conditions, and the cellular stimuli engaged. Thus, we will discuss the mechanisms and cellular responses by which extracellular RNAs operate between defense and disease. Finally, natural counteracting molecules, such as RNase1, will be focused on to elaborate their protective functions in the context of inflammatory and ischemic cardiovascular diseases with the possibility to apply them as novel interventional strategies.