Neutrophil proteome shifts over the myocardial infarction time continuum.
Michael J DasekeFritz M ValerioWilliam J KaluscheYonggang MaKristine Y DeLeon-PennellMerry L LindseyPublished in: Basic research in cardiology (2019)
In response to myocardial infarction (MI), neutrophils (PMNs) are early responders that initiate the inflammatory reaction. Because macrophages and fibroblasts show polarization states after MI, we hypothesized PMNs also undergo phenotypic changes over the MI time course. The objective of the current study was to map the continuum of polarization phenotypes in cardiac neutrophils over the first week of MI. C57BL/6J male mice (3-6 months old) underwent permanent coronary artery ligation to induce MI, and PMNs were isolated from the infarct region at days 1, 3, 5, and 7 after MI. Day 0 served as a no MI negative control. Aptamer proteomics was performed on biological replicates (n = 10-12) for each time point. Day (D)1 MI neutrophils had a high degranulation profile with increased matrix metalloproteinase (MMP) activity. D3 MI neutrophil profiles showed upregulation of apoptosis and induction of extracellular matrix (ECM) organization. D5 MI neutrophils further increased their ECM reorganization profile. D7 MI neutrophils had a reparative signature that included expression of fibronectin, galectin-3, and fibrinogen to contribute to scar formation by stimulating ECM reorganization. Of note, fibronectin was a key modulator of degranulation, as it amplified MMP-9 release in the presence of an inflammatory stimulus. Our results indicate that neutrophils selectively degranulate over the MI time course, reflective of both their intrinsic protein profiles as well as the ECM environment in which they reside. MMPs, cathepsins, and ECM proteins were prominent neutrophil degranulation indicators.
Keyphrases
- extracellular matrix
- coronary artery
- heart failure
- oxidative stress
- poor prognosis
- left ventricular
- clinical trial
- cell proliferation
- randomized controlled trial
- coronary artery disease
- mass spectrometry
- cell death
- signaling pathway
- binding protein
- acute myocardial infarction
- protein protein
- acute coronary syndrome
- percutaneous coronary intervention
- study protocol