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Published on: February 17, 2013
Long noncoding RNA profile of the intracranial artery in patients with moyamoya disease
Takashi Mamiya1, Fumiaki Kanamori1, Kinya Yokoyama1
11Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya.
Objective:
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions.
Methods:
The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions.
Results:
The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis.
Conclusions:
The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.
Insights
Researchers identified distinct long noncoding RNA (lncRNA) expression profiles in Moyamoya disease (MMD) lesions, revealing potential new insights into this rare cerebrovascular disorder and its pathogenesis.
Area of Science:
- Vascular Biology
- Genomics
- Molecular Medicine
Background:
- Moyamoya disease (MMD) is a rare cerebrovascular condition causing progressive stenosis of the internal carotid artery (ICA) and formation of collateral vessels.
- The underlying pathogenesis of MMD remains largely unknown.
- Long noncoding RNAs (lncRNAs) are critical regulators of gene expression and are implicated in various vascular diseases, but their role in MMD is unexplored.
Purpose of the Study:
- To investigate the lncRNA expression profile in Moyamoya disease lesions.
- To identify differentially expressed lncRNAs in MMD compared to normal cerebral arteries.
- To predict the biological functions associated with these lncRNAs in MMD pathophysiology.
Main Methods:
- Microsamples of the middle cerebral artery (MCA) were collected from MMD patients (n=21) and controls (n=11).
- Microarray experiments were performed to compare lncRNA expression profiles.
- Differentially expressed lncRNAs (fold change > 2, q < 0.05) and their cis-regulated coding genes were identified, followed by Gene Ontology (GO) analysis.
Main Results:
- A total of 308 differentially expressed lncRNAs were detected in MMD lesions, with 306 upregulated and 2 downregulated.
- GO analysis of cis-regulated coding genes suggested involvement in immune responses (antibacterial, T-cell receptor signaling) and blood vessel development (cytokine regulation, morphogenesis).
Conclusions:
- The lncRNA expression profile in MMD lesions differs significantly from normal cerebral arteries.
- Identification of differentially expressed lncRNAs provides novel insights into the pathophysiology of Moyamoya disease.
- This research opens avenues for understanding MMD pathogenesis and potential therapeutic targets.
