Intracellular and Extracellular miRNAs in Regulation of Angiogenesis Signaling.

Angiogenesis, the process by which new blood vessels are formed, is a critical phenomenon that is activated during various stages of mammalian development. MicroRNAs (miRNAs), a class of short, single stranded, non-coding RNAs, are recognized as important regulators of angiogenesis, and the role of intracellular miRNAs in modulating angiogenesis signaling has been identified. The recent discovery of extracellular and circulating miRNAs has sparked new questions regarding their potential in modulating angiogenesis signaling not only within cells but also between cells. In this review, we discuss the characteristics of intracellular and extracellular miRNAs and decipher the potential functional roles for these molecules in regard to the angiogenic process. We summarize what is currently known about circulating miRNAs in distinct clinical populations and discuss evidence that implicates extracellular miRNAs as novel mediators of angiogenesis-associated intercellular signaling. Lastly, we offer a new perspective on the functional role of vesicle-encapsulated circulating miRNA in modulating angiogenesis signaling pathways.