Abstract Details

Title Novel Transcripts miR-1301, miR-130, and miR-629 Influence Early Neurologic Outcome in Acute Ischemic Stroke Patients

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S22 - Stroke Genetics, Cellular Responses, and Animal Models (3:41 PM-3:52 PM)

Poster/Presentation
Number 002

Objective

Identify time dependent miRNA-mRNA transcript interactions in acute ischemic stroke (AIS) patients influence by time and early changes in ischemic volume (ECS), an imaging biomarker of response to thrombolysis and early neurologic improvement (ENI).

Background Micro RNA (miRNA) regulate gene transcription induced by cerebral ischemia. Currently, time dependency and the influence of thrombolysis on such miRNA expression and downstream effects on gene transcription and clinical outcome is unknown.

Design/Methods Enrolled patients (n=22) had MRI and blood sample collection at baseline, 2-hours, and 24-hours post baseline MRI. Blood samples from patients with a known last seen normal (LSN) up to 24 hours were analyzed, excluding post-thrombolysis samples to select time dependent miRNA. ECS (difference in ischemic volume before and 2-hour post-thrombolysis) were measured using automated co-registered MRI sequences and correlated with transcript profiles collected 2-hours post-thrombolysis. RNA-Seq was performed with HiSeq 25000 Illumina platform. After correcting for age, gender, and race, leave one out testing was used to select transcripts that correlated with the ECS or time from LSN (FDR corrected P-value < 0.05). IPA Ingenuity MicroRNA filter was used to identify miRNA-mRNA interactions.

Results

Transcripts miR-1301 and miR-629 positively and miR-130 negatively correlated with LSN and had miRNA-mRNA interactions with 4 mRNA transcripts that significantly correlated with ECS (lactate dehydrogenase A, solute carrier family 44 member 1, ubiquitin specific peptidase 33, and dual specificity phosphatase 3). These mRNA negatively correlated with ECS, meaning patients with larger reductions in ischemic volume were less likely to have the following expected downstream effects from these miRNA-mRNA interactions reported in the literature, including, hypoxia inducible factor-1 alpha degradation, thrombus formation, abnormal glutamate clearance, blood brain barrier disruption, cerebral edema, and angiogenesis.

Conclusions

We report 3 novel miRNA selected by MRI biomarker of ENI that may have potential as unique therapeutic targets in AIS patients.

Authors/Disclosures
Alexis N. Simpkins, MD, PhD, MSCR, FAAN (Cedars-Sinai Medical Center, Dept of Neurology) PRESENTER	Dr. Simpkins has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for National Institute of Neurological Disorders and Stroke Data Safety Monitoring Board. Dr. Simpkins has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stroke: Vascular and Interventional Neurology. The institution of Dr. Simpkins has received research support from NIH/NIA. The institution of Dr. Simpkins has received research support from Bristol-Meyer Squibb Foundation. Dr. Simpkins has received publishing royalties from a publication relating to health care.
	No disclosure on file
Zurab Nadareishvili, MD, PhD (George Washington University, Department of Neurology)	No disclosure on file
	No disclosure on file
Richard Leigh, MD (Johns Hopkins University)	The institution of Dr. Leigh has received research support from National Institutes of Health. The institution of Dr. Leigh has received research support from American Heart Association. Dr. Leigh has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Richard T. Benson, MD, PhD, FAAN (National Institute of Neurological Disorders and Stroke)	Dr. Benson has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Journals (AAN). Dr. Benson has received personal compensation in the range of $100,000-$499,999 for serving as a Federal employee with HHS/NIH.
Amie W. Hsia, MD (MedStar Health / MedStar Washington Hospital Center)	The institution of Dr. Hsia has received research support from NIH/NINDS.
John K. Lynch, DO, MPH (NINDS)	Dr. Lynch has nothing to disclose.
John M. Hallenbeck, MD (Chief Stroke Branch NIH)	No disclosure on file
	No disclosure on file

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