Proteomics Reveals Neutrophil Markers Of Infarct Wall Thinning

Neutrophils infiltrate early in myocardial infarction (MI) to initiate necrotic debris removal by launching a proinflammatory response. The extent of cardiomyocyte necrosis within the first 24 h of MI establishes the degree of wall thinning that will occur in the infarct zone. As neutrophils coordinate early tissue remodeling by degranulating proteases to oversee tissue breakdown, we hypothesized neutrophil protein expression might mirror the extent of infarct wall thinning at MI day 1. We examined a dataset collected following permanent coronary artery ligation in 3-6 months old C57BL/6J male mice. The dataset included echocardiography assessment of wall thickness and aptamer-based proteomic evaluation of neutrophils isolated from the left ventricle of control day 0 (n=10) or MI day 1 (n=10) mice. The wall thinning index was calculated as 1/wall thickness; all analyses were performed as comparisons to infarct wall thickness at systole. By regression analysis of 123 neutrophil proteins to wall thinning index at both day 0 and MI day 1, there were 4 proteins positively associated, with all 4 proteins increasing with greater wall thinning. These were histone H1.2 (r=0.62, p=0.004), S100A9 (r=0.60, p=0.005), histone H3.1 (r=0.55, p=0.01), and fibrinogen (r=0.47, p=0.04). Our results reveal protein candidates that may be therapeutic targets to limit MI wall thinning.