Mapping neutrophil polarization over the myocardial infarction time continuum

Abstract

In response to myocardial infarction (MI), neutrophils are early responders that initiate the inflammatory reaction. However, whether they have other roles in cardiac wound healing has not been explored. We hypothesized that neutrophils may undergo polarization state changes over the MI time course. C57BL/6J male mice (3–6 months old) were subjected to permanent coronary artery ligation to induce MI, and neutrophils were isolated from the infarct region at days, 1, 3, 5, and 7 after MI. Day 0 served as negative no MI controls. Aptamer proteomics was performed on n=10–12 biological replicates for each time, and a total of 123 proteins passed quality control and were assessed. Day 1 MI neutrophils exhibited upregulation of cytokine signaling pathways (IL‐16), extracellular matrix (ECM) degradation (MMP‐8 and MMP‐9), and leukocyte recruitment (calgranulin B). Day 3 MI neutrophils exhibited a similar phenotype, with an increase in ECM reorganization and fibrinolysis (activin A, cathepsin D, and fibrinogen). At MI days 5 and 7, neutrophils displayed a more pronounced shift to ECM reorganization indicated by the continued increase in proteins directly involved in fibrotic pathways (fibrinogen, fibronectin, galectin‐3, and vitronectin). Our results indicate neutrophils show distinct protein expression profiles over the first week of MI. This is the first report to detail the changes in the neutrophil proteome over the first week of MI.Support or Funding InformationNIH GM104357, GM114833, GM115428, HL051971, HL075360, HL129823, and VA 5I01BX000505This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.