Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs

Korostyński, Michał; Morga, Rafał; Piechota, Marcin; Hoinkis, Dżesika; Gołda, Sławomir; Dziedzic, Tomasz; Słowik, Agnieszka; Moskała, Marek; Pera, Joanna

doi:10.1007/s12035-019-01789-1

Cited by 17 publications

(22 citation statements)

References 40 publications

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“…Various miRNAs have been identified as key regulators that modulate the pathogenesis of aneurysm [ 51 , 52 ]. In our results, miR-26b-5p and miR-335-5p were highlighted.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of common key genes and pathways of intracranial, abdominal, and thoracic aneurysms

Liu

et al. 2021

BMC Cardiovasc Disord

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Background Aneurysm is a severe and fatal disease. This study aims to comprehensively identify the highly conservative co-expression modules and hub genes in the abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA) and intracranial aneurysm (ICA) and facilitate the discovery of pathogenesis for aneurysm. Methods GSE57691, GSE122897, and GSE5180 microarray datasets were downloaded from the Gene Expression Omnibus database. We selected highly conservative modules using weighted gene co‑expression network analysis before performing the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and Reactome enrichment analysis. The protein–protein interaction (PPI) network and the miRNA-hub genes network were constructed. Furtherly, we validated the preservation of hub genes in three other datasets. Results Two modules with 193 genes and 159 genes were identified as well preserved in AAA, TAA, and ICA. The enrichment analysis identified that these genes were involved in several biological processes such as positive regulation of cytosolic calcium ion concentration, hemostasis, and regulation of secretion by cells. Ten highly connected PPI networks were constructed, and 55 hub genes were identified. In the miRNA-hub genes network, CCR7 was the most connected gene, followed by TNF and CXCR4. The most connected miRNAs were hsa-mir-26b-5p and hsa-mir-335-5p. The hub gene module was proved to be preserved in all three datasets. Conclusions Our study highlighted and validated two highly conservative co-expression modules and miRNA-hub genes network in three kinds of aneurysms, which may promote understanding of the aneurysm and provide potential therapeutic targets and biomarkers of aneurysm.

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“…Various miRNAs have been identified as key regulators that modulate the pathogenesis of aneurysm [ 51 , 52 ]. In our results, miR-26b-5p and miR-335-5p were highlighted.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of common key genes and pathways of intracranial, abdominal, and thoracic aneurysms

Liu

et al. 2021

BMC Cardiovasc Disord

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“…It is known that rupture of an intracranial aneurysm and consequential subarachnoid hemorrhage results in diffuse systemic pathology and, importantly, appears to modulate immunobiology. 11-14 Moreover, there is evidence to suggest that the products of erythrocyte degradation within the subarachnoid space ultimately initiate an inflammatory cascade as well as a state of relative immunodepression. 11-14 Indeed, intracranial aneurysmal rupture is unlikely to directly cause the inception of a malignant process such as atypical lymphoid proliferations of the basal ganglia described herein.…”

Section: Discussionmentioning

confidence: 99%

“…11-14 Moreover, there is evidence to suggest that the products of erythrocyte degradation within the subarachnoid space ultimately initiate an inflammatory cascade as well as a state of relative immunodepression. 11-14 Indeed, intracranial aneurysmal rupture is unlikely to directly cause the inception of a malignant process such as atypical lymphoid proliferations of the basal ganglia described herein. However, we hypothesize that consequences of uncontrolled neuroinflammation and resultant immunodepression from aneurysmal rupture may have allowed a pre-existing atypical lymphoid proliferation to undergo aggressive expansion as depicted in the present case.…”

Section: Discussionmentioning

confidence: 99%

Rapidly Fatal Encephalitis Associated with Atypical Lymphoid Proliferations of the Basal Ganglia Subsequent to Aneurysmal Subarachnoid Hemorrhage

Kar

Guilliams

Cuoco

et al. 2019

Clinics and Practice

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Rapidly fatal encephalitis associated with atypical lymphoid proliferations after intracranial aneurysm rupture has not been reported. Here, we describe a 52-year-old female who presented to the emergency department with a severe headache. Imaging demonstrated aneurysmal subarachnoid hemorrhage due to a ruptured left posterior inferior cerebellar artery aneurysm, which was treated with endovascular embolization and subsequent external ventricular drain. She recovered without neurologic sequelae by day seven; however, five weeks later she represented with a severe headache associated with nausea and fever. Initial repeat imaging was unremarkable. She deteriorated quickly and was empirically treated for meningitis despite negative cerebrospinal fluid studies. Magnetic resonance imaging revealed diffuse cerebral edema within the basal ganglia and thalamus. Biopsy of the caudate nuclei revealed atypical lymphoid proliferations. She was treated accordingly with no significant improvement. This case highlights the necessity for a better understanding of the etiology, chronology, and natural history of atypical lymphoid proliferations.

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“…The sRNA-seq data were submitted to the NCBI Sequence Read Archive (SRA): SRP150595. The detailed analysis of the regulated miRNA has been published elsewhere [9]. In this study, we focus on multiple different classes of sRNAs that are differentially expressed in the blood in response to IA rupture.…”

Section: Blood Collection and Rna Extractionmentioning

confidence: 99%

“…In our previous studies, we focused on the effects exerted by IA rupture on the expression of mRNAs and miRNAs in peripheral blood cells [4,9]. In this preliminary study, we investigated changes in the expression of small ncRNAs other than miRNAs in peripheral blood cells using deep transcriptome sequencing in a single cohort of patients.…”

Section: Introductionmentioning

confidence: 99%

Opposite regulation of piRNAs, rRNAs and miRNAs in the blood after subarachnoid hemorrhage

et al. 2020

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Multiple classes of small RNAs (sRNAs) are expressed in the blood and are involved in the regulation of pivotal cellular processes. We aimed to elucidate the expression patterns and functional roles of sRNAs in the systemic response to intracranial aneurysm (IA) rupture. We used next-generation sequencing to analyze the expression of sRNAs in patients in the acute phase of IA rupture (first 72 h), in the chronic phase (3-15 months), and controls. The patterns of alterations in sRNA expression were analyzed in the context of clinically relevant information regarding the biological consequences of IA rupture. We identified 542 differentially expressed sRNAs (108 piRNAs, 99 rRNAs, 90 miRNAs, 43 scRNAs, 36 tRNAs, and 32 snoRNAs) among the studied groups with notable differences in upregulated and downregulated sRNAs between the groups and sRNAs categories. piRNAs and rRNAs showed a substantial decrease in RNA abundance that was sustained after IA rupture, whereas miRNAs were largely upregulated. Downregulated sRNA genes included piR-31080, piR-57947, 5S rRNA, LSU-rRNA, and SSU-rRNA s. Remarkable enrichment in the representation of transcription factor binding sites was revealed in genomic locations of the regulated sRNA. We found strong overrepresentation of glucocorticoid receptor, retinoid x receptor alpha, and estrogen receptor alpha binding sites at the locations of downregulated piRNAs, tRNAs, and rRNAs. This report, although preliminary and largely proof-of-concept, is the first to describe alterations in sRNAs abundance levels in response to IA rupture in humans. The obtained results indicate novel mechanisms that may constitute another level of control of the inflammatory response. Key messages & A total of 542 sRNAs were differentially expressed after aneurysmal SAH comparing with controls & piRNAs and rRNAs were upregulated and miRNAs were downregulated after IA rupture & The regulated sRNA showed an enrichment in the representation of some transcription factor binding sites & piRNAs, tRNAs, and rRNAs showed an overrepresentation for GR, RXRA, and ERALPHA binding sites

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Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs

Cited by 17 publications

References 40 publications

Bioinformatics analysis of common key genes and pathways of intracranial, abdominal, and thoracic aneurysms

Bioinformatics analysis of common key genes and pathways of intracranial, abdominal, and thoracic aneurysms

Rapidly Fatal Encephalitis Associated with Atypical Lymphoid Proliferations of the Basal Ganglia Subsequent to Aneurysmal Subarachnoid Hemorrhage

Opposite regulation of piRNAs, rRNAs and miRNAs in the blood after subarachnoid hemorrhage

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