From the Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany (A.Z.); and Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
Circ Res. 2016 Feb 5;118(3):469-79. doi: 10.1161/CIRCRESAHA.115.307961.
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.
在西方世界，炎症和缺血性心血管疾病（尤其是动脉粥样硬化和心肌梗死）仍然是头号死因，而目前可用的治疗选择仍然有限。最近的一些发现表明，核酸，特别是细胞外核糖体 RNA 和 microRNAs，对动脉粥样硬化、心肌梗死和其他心血管疾病的不良预后有重要贡献。细胞外 RNA 作为新型危险相关分子模式信号和心血管炎症和血栓形成的有效辅助因子，特别是在组织损伤或病理条件下在细胞外空间积累时。在这篇简明的综述文章中，将讨论细胞外 RNA 的不同实体、它们的细胞来源以及它们对心血管疾病发病机制的潜在功能贡献。事实上，这些带负电荷的分子在细胞外促进防御反应和引发心血管疾病发展之间存在着微妙的平衡，这取决于它们的浓度、环境条件和所涉及的细胞刺激。因此，我们将讨论细胞外 RNA 在防御和疾病之间发挥作用的机制和细胞反应。最后，将集中讨论天然拮抗分子，如 RNase1，以阐述它们在炎症和缺血性心血管疾病中的保护作用，并有可能将其作为新的介入策略加以应用。
