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 day 1 in the mouse model of MI. To understand the correlation, we examined a previously published data set that included day 0 (n = 10) and MI day (D) 1 (n = 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 (r = 0.62, P = 0.004), S100A9 (r = 0.60, P = 0.005), histone 3.1 (r = 0.55, P = 0.01), and fibrinogen (r = 0.47, P = 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, n = 7 M (D1), and n = 5 M (D3)] and compared with saline vehicle control-treated mice [n = 6 M (D1) and n = 6 M (D3)] at MI days 1 and 3. At MI day 3, the S100A8/A9 group showed a 22% increase in the wall thinning index compared with saline (P = 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 day 1 and increased macrophage infiltration at D3. Our results reveal that S100A9 is a functional effector of infarct wall thinning.