Regulation of Atherosclerosis by microRNAs
Our knowledge in the role of small non-coding RNA molecules in the regulation of tissue homeostasis and disease in the cardiovascular system is steadily growing. Among this group of RNA molecules, microRNAs (miRNAs) fulfill important functions in cellular behavior of endothelial cells, vascular smooth muscle cells, and macrophages by influencing the protein output levels of a high variety of genes with crucial outcomes in the atherosclerotic setting. For example, miR- 155 can intensify early stages of atherosclerosis by increasing inflammatory activation and inefficient lipid handling in macrophages. However, miRNAs display also important atheroprotective roles as demonstrated for the complementary strands of miR-126, which form a dual system sustaining the endothelial proliferative reserve and promoting endothelial regeneration to counteract atherogenic effects of disturbed flow and hyperlipidemia.
Excitingly, miRNA functions are not restricted to the producing cells but can be transferred to other cells by secretion and transport within extracellular vesicles including exosomes and microvesicles. Moreover, circulating miRNAs are found in the blood stream stabilized by complex formation with lipoproteins and ribonucleoprotein complexes. Once incorporated by the recipient cells, these extracellular miRNAs regulate target mRNAs thereby acting as a new gadget in cell-cell communication also in atherosclerosis. This chapter provides novel concepts on regulatory mechanisms of miRNAs including the function of RNA sponges, miRNA tandems, and the complementary role of miRNA strand pairs and discusses their diagnostic and therapeutic potential in atherosclerosis.