Korean J Neurotrauma.  2013 Oct;9(2):41-46. 10.13004/kjnt.2013.9.2.41.

Identification of MicroRNAs with Altered Expression Profiles in a Rat Model of Experimentally Induced Early Cerebral Aneurysms

• Jeong SH
• Lee HJ
• Yi JS
• Lee HJ
• Lee IW
• Park KC
• Yang JH

• KMID: 2156098
• DOI: http://doi.org/10.13004/kjnt.2013.9.2.41

Abstract

OBJECTIVE
Structural adaptation of the vascular wall may occur due to various factors, such as shear stress, pressure, injury or inflammation. The role of microRNAs (miRNAs) in the development of vascular remodeling has been investigated in several studies. Recently, the authors reported altered expression profiles of miRNAs in late stage of experimentally induced giant cerebral aneurysm (CA) in rat models. But, early biologic roles of miRNAs in CA formation have not been explained yet. We employed microarrays analysis to identify miRNA expression profiles in early stage of CA in rat model and to compare with those in late stage of giant CA.
METHODS
Seventy, 7-week-old male Sprague-Dawley rats underwent a CA induction procedure. The control animals (n=11) were fed a regular diet, and the experimental animals (n=59) were fed a regular diet with 1% normal saline for two months. Then, the rats were killed, their cerebral arteries were dissected, and the 13 regions of early aneurysmal change on the right olfactory artery-anterior cerebral artery bifurcation were cut for miRNA microarrays analysis. Six miRNAs (miRNA-1, miRNA-448, miRNA-352, miRNA-551b, miRNA-431, and miRNA-485) were randomly chosen for validation using real-time quantitative polymerase chain reaction.
RESULTS
Among a set of differentially expressed miRNAs, 15 miRNAs were up-regulated more than 200% and five miRNAs were down-regulated less than 50% in the early CA tissues.
CONCLUSIONS
This study provides an overall view of miRNA expression profiles in experimentally induced early CAs and strongly supports the idea that some miRNAs, such as miR-31 and miR-27a, play an important role in pathological processes in early CA formation. Further investigations to detect their exact roles of these miRNAs in the pathogenesis of CA are needed.

Keyword

Intracranial aneurysm; MicroRNAs; Vascular remodelling; Smooth muscle cell; Endothelial cell; Macrophage

MeSH Terms

Aneurysm
Animals
Cerebral Arteries
Diet
Endothelial Cells
Humans
Inflammation
Intracranial Aneurysm*
Macrophages
Male
MicroRNAs*
Models, Animal*
Myocytes, Smooth Muscle
Pathologic Processes
Rats*
Rats, Sprague-Dawley
MicroRNAs

Figure

• 

  FIGURE 1. Two months after the induction procedures. The aneurysm samples of different stages were obtained from the right olfactory artery-anterior cerebral artery (OA-ACA) bifurcation area. A: Normal OA-ACA bifurcation. B: Early cerebral aneurysm at OA-ACA bifurcation (black arrowhead). C: Advanced cerebral aneurysm at OA-ACA bifurcation (black arrowhead). ACA: anterior cerebral artery, OA: olfactory artery (×400 magnification).

• 

  FIGURE 2. Hierarchical clustering analysis of miRNA expression of early cerebral aneurysms and control cerebral arteries. miRNAs are presented in rows and samples are presented in columns. Colors indicate relative signal intensities; red and blue colors indicate up-expressed and down-expressed miRNAs, respectively.

• 

  FIGURE 3. Summary of real-time quantitative polymerase chain reaction (qPCR) analysis for the up-expressed miRNAs (miRNA-1, miRNA-448, and miRNA-352) and the down-expressed miRNAs (miRNA-551b, miRNA-431, and miRNA-485). Six randomly selected miRNAs are listed on the x-axis, and relative expression levels are placed on the y-axis as up and down direction. ∗significant difference between CAs and control arteries (p<0.05). CA: cerebral aneurysm.

Reference

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