Abstract 14406: A Novel Population of Neutrophils, Low Density Granulocytes, Are Upregulated in Acute ST Segment Elevation Myocardial Infarction
Introduction: Neutrophils (PMNs) are known to play a role in atherosclerosis, however, whether they are modulated during STEMI is unknown due to the difficulty in obtaining these cells ex vivo before they activate. Neutrophil extracellular traps (NETs) bearing tissue factor have been implicated in STEMI. Low density granulocytes (LDGs), a subset of pro-inflammatory PMNs first identified in inflammatory diseases such as lupus, have an enhanced ability to form NETs. Whether PMNs are modulated during STEMI and whether LDGs are present during STEMI is unknown. This understanding may augment future therapies targeting these mediators.
Methods: A prospective analysis of arterial blood samples obtained from patients presenting with STEMI (n=33) to a single primary percutaneous coronary intervention center was performed. Healthy, age-matched subjects without cardiovascular risk factors were used as controls (n=17). A Ficoll gradient was used to isolate peripheral blood mononuclear cells. LDGs were identified using flow cytometry with cell surface markers CD15+/CD14lo. Levels of inflammatory cytokines involved in PMN modulation including IL-1β, IL-6, IL-18 and IL-8 were measured. The relationship between inflammatory cytokine levels and frequency of LDGs was analyzed using unadjusted and adjusted multivariable regression.
Results: In this pilot study, we found median elevations in inflammatory cytokines IL-1β (5.06 pg/mL vs 0.07 pg/mL), IL-6 (11 pg/mL vs 0.64 pg/mL), IL-18 (411.05 pg/mL vs 67.14 pg/mL) and IL-8 (26 pg/mL vs 5 pg/mL) in STEMI compared to healthy controls (p<0.001 for all). Furthermore, mean frequency of PMNs was higher (10.3% vs 3.49%; p=0.001), and strikingly, a median increase of 39% in LDGs was detected in STEMI, which remained associated with STEMI after adjustment for age, sex and CV risk factors (β=0.45, p = 0.014). Finally, S100A8/A9, a protein known to augment NETs and PMN chemotaxis, was elevated in STEMI (289 ng/mL vs 192 ng/dl, p=0.01).
Conclusions: Inflammatory cytokines are upregulated during STEMI, with an increase in PMNs and S100A8/A9. Furthermore, LDGs are present during STEMI, independent of CV risk factors. Future studies on the role of PMNs and subsets of LDGs may potentiate neutrophil-targeted therapies in acute STEMI.
Author Disclosures: J.H. Kim: None. H. Teague: None. A.K. Dey: None. A.A. Joshi: None. R. Yunus: None. J.B. Lerman: None. T.M. Aberra: None. A. Chaturvedi: None. Q. Ng: None. J. Silverman: None. T. Aridi: None. M.P. Playford: None. R. Mazhari: None. N. Mehta: None.
- © 2016 by American Heart Association, Inc.