Understanding the Role of microRNAs in the Pathogenesis of Intracranial Aneurysms

Review Article

J Dis Markers. 2015; 2(4): 1033.

Understanding the Role of microRNAs in the Pathogenesis of Intracranial Aneurysms

Wright MC, Medel R, Dumont AS and Amenta PS*

Department of Neurosurgery, Tulane University Medical Center, New Orleans, USA

*Corresponding author: Amenta PS, Department of Neurosurgery, Tulane University Medical Center, New Orleans, USA

Received: October 15, 2015; Accepted: November 12, 2015; Published: November 17, 2015


Treatment options 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.

Keywords: Intracranial aneurysms; microRNA; Genetic markers


IA: Intracranial Aneurysms; 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.


Intracranial aneurysms (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 [1-3]. 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 [4]. Current microsurgical and endovascular treatment of IAs remains associated with significant risk, which may exceed the annual risk of rupture [5]. 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.

Currently, establishing the risk of rupture for an individual aneurysm is imprecise and depends on morphologic features of the aneurysm and an assessment of the clinical history of the patient. Aneurysm location, irregularities of the aneurysm dome, and size remain the most relied upon features, with increasing size and posterior circulation location being associated with a higher risk. The clinical picture of the individual patient also contributes to decision making, as a history of hypertension, smoking, alcohol abuse, and positive family history increase the risk of rupture [1].

In an attempt to overcome the limitations of the current methodology, there has been a concerted effort to further delineate the mechanisms of aneurysm formation, growth, and rupture. These investigations have largely focused on the molecular and cellular pathways involved in vascular disease, including, the chronic and pathologic inflammatory response, hemodynamic stress, and the identification of predictive biomarkers. Furthermore, the recognition of genetic markers associated with IAs has played an increasingly important role in the understanding of their pathogenesis. microRNAs (miRNAs) represent one such class of molecular regulating molecules involved in the gene expression underlying aneurysm formation (Table 1).

Citation:Wright MC, Medel R, Dumont AS and Amenta PS. Understanding the Role of microRNAs in the Pathogenesis of Intracranial Aneurysms. J Dis Markers. 2015; 2(4): 1033. ISSN:2380-0682