Abstract Details

Title Genomic Analysis of Leukocyte mRNA Suggests Immune Predisposition to Hemorrhagic Transformation in Ischemic Stroke

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S41 - (-)

Poster/Presentation
Number 006

Objective

Background Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood brain barrier is a central feature to HT pathogenesis, and leukocytes may contribute to this process. We sought to.

Design/Methods Stroke patient blood samples were obtained prior to treatment with thrombolysis, and leukocyte RNA assessed by microarray analysis. Strokes that developed HT (n=11) were compared to strokes without HT (n=33) and controls (n=14). Genes were identified (corrected p-value <0.05, fold change >|1.2|) and functional analysis performed. RNA prediction of HT in stroke was evaluated using cross-validation, and in a second stroke cohort (n=23).

Results Ichemic strokes that developed HT had differential expression of 29 genes in circulating leukocytes prior to treatment with thrombolytic. A panel of 6 genes could predict strokes that later developed HT with 86.4% accuracy. Key pathways involved in HT of human stroke are described, including amphiregulin, a growth factor that regulates matrix metalloproteinase-9; a shift in transforming growth factor-beta signaling involving SMAD4, INPP5D and IRAK3; and a disruption of coagulation factors V and VIII.

Conclusions Identified genes correspond to differences in inflammation and coagulation that may predispose to HT in ischemic stroke. Given the adverse impact of HT on stroke outcomes, further evaluation of identified genes and pathways is warranted to determine their potential as therapeutic targets to reduce HT and as markers of HT risk.

Authors/Disclosures
Glen Jickling, MD PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Piero Verro, MD	No disclosure on file
	No disclosure on file
Edward C. Jauch, MD, MS, FAHA, FACEP (Medical University of South Carolina)	No disclosure on file
	No disclosure on file
Joseph P. Broderick, MD, FAAN (University of Cincinnati)	Dr. Broderick has received publishing royalties from a publication relating to health care.
Frank R. Sharp, MD (University of California at Davis)	No disclosure on file

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