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 |
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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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