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International Stroke Conference Poster Abstracts
Session Title: Health Services, Quality Improvement, and Patient-Centered Outcomes Posters II

Abstract TP274: HMGB1 is Regulated by Microrna in Patients With Ischemic Stroke

Originally publishedhttps://doi.org/10.1161/str.49.suppl_1.TP274Stroke. 2018;49:ATP274

    Background: High mobility group box 1 (HMGB1) is a strong inducer of inflammatory pathways in ischemic stroke, and a marker of worse neurological outcome at 1 year. As such HMGB1 may contribute to secondary brain injury and decline in ischemic stroke. We sought to understand the regulation of HMGB1 by microRNA in patients with ischemic stroke and the relationship to stroke severity.

    Methods: In 106 ischemic stroke patients and 106 vascular risk factor controls levels of HMGB1 were compared in relationship to levels of microRNA. HMGB1 in plasma was measured by ELISA. microRNA isolated from circulating leukocytes were measured by microarray and confirmed by RT-PCR. HMGB1 regulation by identified microRNA were assessed both in-silico and in-vitro by luciferase assay.

    Results: HMGB1 is increased in ischemic stroke patients compared to controls (p<0.05) in a manner that is related to severity of stroke. An increase in admission NIHSS is associated with an increase in HMGB1. The increase in HMGB1 corresponded with a decreased in microRNA let7i. Direct regulation of HMGB1 was shown for microRNA let7i. When HMGB1 levels were adjusted for let7i, the association with NIHSS was no longer present.

    Conclusions: HMGB1 is increased in patients with stroke and correlates with stroke severity. microRNA regulate HMGB1 in patients with stroke and may be an important mediator of immune activation associated with secondary ischemic brain injury.

    Footnotes

    Author Disclosures: G. Jickling: Research Grant; Significant; AHA, NIH. B.P. Ander: None. N. Shroff: None. F. Hamade: None. B. Stamova: None. C. Dykstra-Aiello: None. D. Liu: Research Grant; Significant; NIH. F.R. Sharp: Research Grant; Significant; NIH.

    This research has received full or partial funding support from the American Heart Association, National Center.

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