Genome-Wide Analysis of the Circulating miRNome After Cerebral Ischemia Reveals a Reperfusion-Induced MicroRNA Cluster

Autor: Roland Veltkamp, Ana Teixeira, Agnes Hotz-Wagenblatt, Ehsan Javidi, Sarah Lamble, Stefan Uhlmann, Karl-Heinz Glatting, Eva Mracsko
Přispěvatelé: St Marys Development Trust
Rok vydání: 2017
Předmět:
MECHANISM
Male
0301 basic medicine
Pathology
BLOOD
INTRACEREBRAL HEMORRHAGE
Brain Ischemia
Mice
0302 clinical medicine
Medicine
EXPERIMENTAL STROKE
Stroke
Pathophysiology
Up-Regulation
Reverse transcription polymerase chain reaction
Multigene Family
Reperfusion Injury
Cardiology and Cardiovascular Medicine
Life Sciences & Biomedicine
serotonin receptor
EXPRESSION
medicine.medical_specialty
Clinical Neurology
INHIBITION
Ischemia
1102 Cardiovascular Medicine And Haematology
CONTRIBUTES
03 medical and health sciences
Downregulation and upregulation
microRNA
Animals
Cerebral Hemorrhage
Advanced and Specialized Nursing
Intracerebral hemorrhage
Science & Technology
TRANSIENT FOCAL ISCHEMIA
Neurology & Neurosurgery
business.industry
1103 Clinical Sciences
medicine.disease
Mice
Inbred C57BL
MicroRNAs
Circulating MicroRNA
030104 developmental biology
Peripheral Vascular Disease
Reperfusion
Cardiovascular System & Cardiology
T-CELLS
Neurosciences & Neurology
Neurology (clinical)
1109 Neurosciences
business
Biomarkers
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: Stroke. 48:762-769
ISSN: 1524-4628
0039-2499
Popis: Background and Purpose— Circulating microRNAs (miRNAs) are emerging biomarkers for stroke because of their high stability in the bloodstream and association with pathophysiologic conditions. However, the circulating whole-genome miRNAs (miRNome) has not been characterized comprehensively in the acute phase of stroke. Methods— We profiled the circulating miRNome in mouse models of acute ischemic and hemorrhagic stroke by next-generation sequencing. Stroke models were compared with sham-operated and naive mice to identify deregulated circulating miRNAs. Top-ranked miRNAs were validated and further characterized by quantitative reverse transcription polymerase chain reaction. Results— We discovered 24 circulating miRNAs with an altered abundance in the circulation 3 hours after ischemia, whereas the circulating miRNome was not altered after intracerebral hemorrhage compared with sham-operated mice. Among the upregulated miRNAs in ischemia, the top-listed miR-1264/1298/448 cluster was strongly dependent on reperfusion in different ischemia models. A time course experiment revealed that the miR-1264/1298/448 cluster peaked in the circulation around 3 hours after reperfusion and gradually decreased thereafter. Conclusions— Alteration of the miRNome in the circulation is associated with cerebral ischemia/reperfusion, but not hemorrhage, suggesting a potential to serve as biomarkers for reperfusion in the acute phase. The pathophysiological role of reperfusion-inducible miR-1264/1298/448 cluster, which is located on chromosome X within the introns of the serotonin receptor HTR2C, requires further investigation.
Databáze: OpenAIRE
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