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Abstract Details

Platelet YES1, PIK3CB, and GNA14 Expression Correlates with Coated-Platelet Levels in Asymptomatic Internal Carotid Stenosis
Cerebrovascular Disease and Interventional Neurology
P1 - Poster Session 1 (5:30 PM-6:30 PM)
3-063

To identify platelet mRNAs correlating with coated-platelet levels in asymptomatic internal carotid stenosis.


Coated-platelets are a subset of procoagulant platelets observed upon dual-agonist stimulation of resting platelets with collagen and thrombin. Elevated coated-platelets predict recurrent large-artery stroke after TIA, and predict incident TIA/stroke among asymptomatic internal carotid stenosis (AICS) patients. Mechanisms determining coated-platelet level variability remain unclear. We now explore platelet gene expression associated with coated-platelet levels in patients with AICS.
Platelet rich plasma from AICS patients was assayed for coated-platelet levels, reported as percentage of cells converted to coated-platelets. Total platelet RNA was sequenced (Illumina HiSeq 3000), aligned (TOPHAT), and counted (HTSeq). We determined genes associated with baseline coated-platelet levels with r>0.5 or <-0.5 and p<0.05 (Spearman’s univariate correlations). Canonical pathways enriched among the genes significantly correlating with coated-platelet levels were determined using Ingenuity Pathway Analysis (IPA).

Twenty-two samples were sequenced, 31,000 transcripts were analyzed, and 147 correlated with baseline coated-platelet levels with r>0.5 or <-0.5. We focused on three transcripts of interest significantly correlated with coated-platelet levels: YES1 (r=0.6, p=0.0033), PIK3CB (r=0.59, p=0.0049), and GNA14 (r=0.52, p=0.013). IPA revealed a significant overlap between three platelet transcripts, YES1, PIK3CB, and GNA14, and canonical pathways associated with tissue factor in angiogenesis and tumor growth in cancer (p=0.0026). 

Our results identified three platelet mRNAs, YES1, PIK3CB, and GNA14, significantly correlating with coated-platelet levels in AICS. Interestingly, YES1 encodes a src family tyrosine kinase that is inhibited by dasatinib, a chemotherapeutic agent for treatment of chronic myelogenous leukemia. A recent study demonstrated lower coated-platelet levels in patients treated with dasatinib who develop bleeding despite normal platelet counts. These findings support a role for this pathway in determining coated-platelet levels, and further study is warranted to understand the specific roles of YES1, PIK3CB and GNA14 in platelet procoagulant potential.


Authors/Disclosures
Angelia Kirkpatrick
PRESENTER
Angelia Kirkpatrick has nothing to disclose.
Eleanor Mathews Eleanor Mathews has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
George Dale George Dale has nothing to disclose.