Abstract 17878: Expression Pattern of Inflammatory Transcripts in Leukocyte Subsets of Acute Coronary Syndrome Patients
Introduction: We have previously shown that an unbiased whole blood gene expression pattern in the acute phase of an acute coronary syndrome (ACS) relates to infarct size. The top transcripts driving this RNA signature included IL1R2, IRAK3, CLEC4E, TLR4 and IFNGR1, key factors in inflammasome signaling. However, it remains unknown what leukocyte subsets drive the expression pattern of these transcripts in whole blood during ACS.
Methods: Peripheral blood monocytes, lymphocytes and neutrophils were isolated from 9 patients in the acute phase of an ACS, at day 3 and at day 30. Monocytes and lymphocytes were isolated by Ficoll density centrifugation followed by CD14 magnetic bead isolation (Miltenyi). Neutrophils were isolated by red blood cell lysis of the lower fraction after Ficoll separation. Real-time PCR was performed using TaqMan primers and normalized to SF3A1 and HPRT1.
Results: IL1R2 and IRAK3 were significantly upregulated in neutrophils on admission and on day 3, compared to stabilization at day 30 (fold change 2.1 and 1.7, p<0.05, figure 1). CLEC4E was upregulated in monocytes (fold change 1.87 and 1.28, p<0.05) and IFNGR1 in lymphocytes (fold change 1.27 and 1.17, p<0.05). However, IFNGR1, CLEC4E and TLR4 also showed a trend towards upregulation in neutrophils. IRAK3 on admission was correlated with infarct size in neutrophils (R2=0.64, p<0.05). IL1R2 and CLEC4E on admission were correlated with infarct size in lymphocytes (R2=0.52 and 0.47, p<0.05), although they were not upregulated in this cell type.
Conclusion: The inflammasome-related transcripts in whole blood during the acute phase in ACS largely originate from neutrophils, but are also identified in other leukocyte subsets. The correlation with infarct size differs according to leukocyte subtype, suggesting that the observed upregulation per individual gene in whole blood most probably results from a cumulative upregulation in distinct leukocyte subsets and an increase in absolute cell count.
Author Disclosures: M. Vanhaverbeke: None. D. Veltman: None. A. Wibowo: None. S. Trenson: None. H. Gillijns: None. H.J. Huber: None. S. Janssens: None. P. Sinnaeve: None.
- © 2016 by American Heart Association, Inc.