Altered Expression of MicroRNA-15a and Kruppel-Like Factor 4 in Cerebrospinal Fluid and Plasma After Aneurysmal Subarachnoid Hemorrhage

Yuichiro Kikkawa, Takeshi Ogura, Hiroyuki Nakajima, Toshiki Ikeda, Ririko Takeda, Hiroaki Neki, Shinya Kohyama, Fumitaka Yamane, Ryota Kurogi, Toshiyuki Amano, Akira Nakamizo, Masahiro Mizoguchi, Hiroki Kurita

Research output: Contribution to journalArticle

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Abstract

Background Cerebral vasospasm (CVS) is a major determinant of prognosis in patients with subarachnoid hemorrhage (SAH). Alteration in the vascular phenotype contributes to development of CVS. However, little is known about the role of microRNAs (miRNAs) in the phenotypic alteration after SAH. We investigated the expression profile of miRNAs and the chronologic changes in the expression of microRNA-15a (miR-15a) and Kruppel-like factor 4 (KLF4), a potent regulator of vascular phenotype modulation that modulates the expression of miR-15a, in the plasma and cerebrospinal fluid (CSF) of patients with SAH. Methods Peripheral blood and CSF samples were collected from 8 patients with aneurysmal SAH treated with endovascular obliteration. Samples obtained from 3 patients without SAH were used as controls in the analysis. Exosomal miRNAs were isolated and subjected to microarray analysis with the three-dimensional-gene miRNA microarray kit. The time course of the expression of miR-15a and KLF4 was analyzed using quantitative real-time polymerase chain reaction. Results Microarray analysis showed that 12 miRNAs including miR-15a were upregulated or downregulated both in the CSF and in plasma after SAH within 3 days. Quantitative real-time polymerase chain reaction showed that miR-15a expression was significantly increased in both the CSF and plasma, with a peak around 3–5 days after SAH, whereas the expression of KLF4 was significantly decreased around 1–3 days after SAH and remained lower than in controls. Conclusions Our results suggest that an early and persistent decrease in KLF4 followed by an increase in miR-15a may contribute to the altered vascular phenotype, resulting in development of CVS.

Original languageEnglish
Pages (from-to)909-916.e3
JournalWorld Neurosurgery
Volume108
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

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Subarachnoid Hemorrhage
MicroRNAs
Cerebrospinal Fluid
Intracranial Vasospasm
Blood Vessels
Microarray Analysis
Phenotype
Real-Time Polymerase Chain Reaction
GKLF protein
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Altered Expression of MicroRNA-15a and Kruppel-Like Factor 4 in Cerebrospinal Fluid and Plasma After Aneurysmal Subarachnoid Hemorrhage. / Kikkawa, Yuichiro; Ogura, Takeshi; Nakajima, Hiroyuki; Ikeda, Toshiki; Takeda, Ririko; Neki, Hiroaki; Kohyama, Shinya; Yamane, Fumitaka; Kurogi, Ryota; Amano, Toshiyuki; Nakamizo, Akira; Mizoguchi, Masahiro; Kurita, Hiroki.

In: World Neurosurgery, Vol. 108, 01.12.2017, p. 909-916.e3.

Research output: Contribution to journalArticle

Kikkawa, Y, Ogura, T, Nakajima, H, Ikeda, T, Takeda, R, Neki, H, Kohyama, S, Yamane, F, Kurogi, R, Amano, T, Nakamizo, A, Mizoguchi, M & Kurita, H 2017, 'Altered Expression of MicroRNA-15a and Kruppel-Like Factor 4 in Cerebrospinal Fluid and Plasma After Aneurysmal Subarachnoid Hemorrhage', World Neurosurgery, vol. 108, pp. 909-916.e3. https://doi.org/10.1016/j.wneu.2017.09.008
Kikkawa, Yuichiro ; Ogura, Takeshi ; Nakajima, Hiroyuki ; Ikeda, Toshiki ; Takeda, Ririko ; Neki, Hiroaki ; Kohyama, Shinya ; Yamane, Fumitaka ; Kurogi, Ryota ; Amano, Toshiyuki ; Nakamizo, Akira ; Mizoguchi, Masahiro ; Kurita, Hiroki. / Altered Expression of MicroRNA-15a and Kruppel-Like Factor 4 in Cerebrospinal Fluid and Plasma After Aneurysmal Subarachnoid Hemorrhage. In: World Neurosurgery. 2017 ; Vol. 108. pp. 909-916.e3.
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abstract = "Background Cerebral vasospasm (CVS) is a major determinant of prognosis in patients with subarachnoid hemorrhage (SAH). Alteration in the vascular phenotype contributes to development of CVS. However, little is known about the role of microRNAs (miRNAs) in the phenotypic alteration after SAH. We investigated the expression profile of miRNAs and the chronologic changes in the expression of microRNA-15a (miR-15a) and Kruppel-like factor 4 (KLF4), a potent regulator of vascular phenotype modulation that modulates the expression of miR-15a, in the plasma and cerebrospinal fluid (CSF) of patients with SAH. Methods Peripheral blood and CSF samples were collected from 8 patients with aneurysmal SAH treated with endovascular obliteration. Samples obtained from 3 patients without SAH were used as controls in the analysis. Exosomal miRNAs were isolated and subjected to microarray analysis with the three-dimensional-gene miRNA microarray kit. The time course of the expression of miR-15a and KLF4 was analyzed using quantitative real-time polymerase chain reaction. Results Microarray analysis showed that 12 miRNAs including miR-15a were upregulated or downregulated both in the CSF and in plasma after SAH within 3 days. Quantitative real-time polymerase chain reaction showed that miR-15a expression was significantly increased in both the CSF and plasma, with a peak around 3–5 days after SAH, whereas the expression of KLF4 was significantly decreased around 1–3 days after SAH and remained lower than in controls. Conclusions Our results suggest that an early and persistent decrease in KLF4 followed by an increase in miR-15a may contribute to the altered vascular phenotype, resulting in development of CVS.",
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T1 - Altered Expression of MicroRNA-15a and Kruppel-Like Factor 4 in Cerebrospinal Fluid and Plasma After Aneurysmal Subarachnoid Hemorrhage

AU - Kikkawa, Yuichiro

AU - Ogura, Takeshi

AU - Nakajima, Hiroyuki

AU - Ikeda, Toshiki

AU - Takeda, Ririko

AU - Neki, Hiroaki

AU - Kohyama, Shinya

AU - Yamane, Fumitaka

AU - Kurogi, Ryota

AU - Amano, Toshiyuki

AU - Nakamizo, Akira

AU - Mizoguchi, Masahiro

AU - Kurita, Hiroki

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background Cerebral vasospasm (CVS) is a major determinant of prognosis in patients with subarachnoid hemorrhage (SAH). Alteration in the vascular phenotype contributes to development of CVS. However, little is known about the role of microRNAs (miRNAs) in the phenotypic alteration after SAH. We investigated the expression profile of miRNAs and the chronologic changes in the expression of microRNA-15a (miR-15a) and Kruppel-like factor 4 (KLF4), a potent regulator of vascular phenotype modulation that modulates the expression of miR-15a, in the plasma and cerebrospinal fluid (CSF) of patients with SAH. Methods Peripheral blood and CSF samples were collected from 8 patients with aneurysmal SAH treated with endovascular obliteration. Samples obtained from 3 patients without SAH were used as controls in the analysis. Exosomal miRNAs were isolated and subjected to microarray analysis with the three-dimensional-gene miRNA microarray kit. The time course of the expression of miR-15a and KLF4 was analyzed using quantitative real-time polymerase chain reaction. Results Microarray analysis showed that 12 miRNAs including miR-15a were upregulated or downregulated both in the CSF and in plasma after SAH within 3 days. Quantitative real-time polymerase chain reaction showed that miR-15a expression was significantly increased in both the CSF and plasma, with a peak around 3–5 days after SAH, whereas the expression of KLF4 was significantly decreased around 1–3 days after SAH and remained lower than in controls. Conclusions Our results suggest that an early and persistent decrease in KLF4 followed by an increase in miR-15a may contribute to the altered vascular phenotype, resulting in development of CVS.

AB - Background Cerebral vasospasm (CVS) is a major determinant of prognosis in patients with subarachnoid hemorrhage (SAH). Alteration in the vascular phenotype contributes to development of CVS. However, little is known about the role of microRNAs (miRNAs) in the phenotypic alteration after SAH. We investigated the expression profile of miRNAs and the chronologic changes in the expression of microRNA-15a (miR-15a) and Kruppel-like factor 4 (KLF4), a potent regulator of vascular phenotype modulation that modulates the expression of miR-15a, in the plasma and cerebrospinal fluid (CSF) of patients with SAH. Methods Peripheral blood and CSF samples were collected from 8 patients with aneurysmal SAH treated with endovascular obliteration. Samples obtained from 3 patients without SAH were used as controls in the analysis. Exosomal miRNAs were isolated and subjected to microarray analysis with the three-dimensional-gene miRNA microarray kit. The time course of the expression of miR-15a and KLF4 was analyzed using quantitative real-time polymerase chain reaction. Results Microarray analysis showed that 12 miRNAs including miR-15a were upregulated or downregulated both in the CSF and in plasma after SAH within 3 days. Quantitative real-time polymerase chain reaction showed that miR-15a expression was significantly increased in both the CSF and plasma, with a peak around 3–5 days after SAH, whereas the expression of KLF4 was significantly decreased around 1–3 days after SAH and remained lower than in controls. Conclusions Our results suggest that an early and persistent decrease in KLF4 followed by an increase in miR-15a may contribute to the altered vascular phenotype, resulting in development of CVS.

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