Understanding the Role of microRNAs in the Pathogenesis of Intracranial Aneurysms

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Treatmentoptions for the management of intracranial aneurysms (IA) remain associated with significant morbidity and mortality. As a result, there is a need to identify biochemical markers predictive of the presence of IAs and the risk of rupture. Genetic factors play a key role in IA pathogenesis, as evidenced by the increased susceptibility to IA formation and rupture in the familial form of the disease. microRNAs (miRNAs), which modulate gene expression, have been demonstrated to be differentially expressed in multiple disease states. To date, little data exists pertaining to miRNA expression and IAs. We review the literature examining miRNA expression and IA formation, progression, and rupture. The relationship between miRNA expression profiles and the specific molecular and cellular processes driving IA genesis are examined. The potential clinical relevance of miRNA is also discussed, as it relates to improving the means by which the risk of rupture is estimated.

IntracranialAneurysms; miRNA: microRNA; aSAH: aneurysmal Subarachnoid Hemorrhage; mRNA; messenger RNA; miRISC: RNA-Induced Silencing Complex; UTR: Untranslated Region; ECM: Extracellular Matrix; TGF-β: Tissue Growth Factor-β; VSMC: Vascular Smooth Muscle Cell; NF-κB: Nuclear Factor-kappa B; IL-6: Interleukin 6; IL-8: Interleukin 8; ICAM-1: Intercellular Adhesion Molecule-1; VCAM-1: Vascular Cell Adhesion Molecule; MMPs: Matrix Metalloproteinases; TIMPs: Tissue Inhibitors of Matrix Metalloproteinases; VEGF: Vascular Endothelial Growth Factor; NF-κB: Nuclear Factor kappa-B; TNF-α: Tumor Necrosis Factor-α; IL-1β: Interleukin-1β; MCP-1: Monocyte Chemo Attractant Protein-1; qPCR: Quantitative PCR; AAA: Abdominal Aortic Aneurysms.

Intracranialaneurysms (IAs) affect 3-6% of the general population and have an annual rupture rate of 1-3%, resulting in approximately 27,000 aneurysmal subarachnoid hemorrhages (aSAH) in the United States each year. The morbidity and mortality of aSAH remains high, with as many as 50% of cases resulting in death, and up to 50% of survivors suffering significant permanent disability. Current microsurgical and endovascular treatment of IAs remains associated with significant risk, which may exceed the annual risk of rupture. Thus, there is a need for both an improved understanding of factors contributing to rupture and the development of noninvasive means by which to identify those aneurysms with a higher risk of rupture.