S100A9 is a functional effector of infarct wall thinning after myocardial infarction.

Neutrophils infiltrate into the left ventricle (LV) early after myocardial infarction (MI) and launch a proinflammatory response. Along with neutrophil infiltration, LV wall thinning due to cardiomyocyte necrosis also peaks at in the mouse model of MI. To understand the correlation, we examined a previously published data set that included ( = 10) and MI () ( = 10) neutrophil proteome and echocardiography assessments. Out of 123 proteins, 4 proteins positively correlated with the infarct wall thinning index (1/wall thickness): histone 1.2 ( = 0.62, = 0.004), S100A9 ( = 0.60, = 0.005), histone 3.1 ( = 0.55, = 0.01), and fibrinogen ( = 0.47, = 0.04). As S100A9 was the highest ranked secreted protein, we hypothesized that S100A9 is a functional effector of infarct wall thinning. We exogenously administered S100A8/A9 at the time of MI to mice [C57BL/6J, male, 3-6 mo of age, = 7 M (), and = 5 M ()] and compared with saline vehicle control-treated mice [ = 6 M () and = 6 M ()] at MI and . At MI , the S100A8/A9 group showed a 22% increase in the wall thinning index compared with saline ( = 0.02), along with higher dilation and lower ejection fraction. The decline in cardiac physiology occurred subsequent to increased neutrophil and macrophage infiltration at MI and increased macrophage infiltration at . Our results reveal that S100A9 is a functional effector of infarct wall thinning. S100A9 is a functional marker of infarct wall thinning.