Pathogenic roles of neutrophil-derived alarmins (S100A8/A9) in heart failure: from molecular mechanisms to therapeutic insights.

An excessive neutrophil count is recognized as a valuable predictor of inflammation and is associated with a higher risk of adverse cardiac events in patients with heart failure (HF). Our understanding of the effectors used by neutrophils to inflict proinflammatory actions needs to be advanced. Recently, emerging evidence has demonstrated a causative role of neutrophil-derived alarmins (i.e., S100A8/A9) in aggravating cardiac injuries by induction of inflammation. In parallel with the neutrophil count, high circulating levels of S100A8/A9 proteins powerfully predict mortality in patients with HF. As such, a deeper understanding of the biological functions of neutrophil-derived S100A8/A9 proteins would offer novel therapeutic insights. Here, the basic biology of S100A8/A9 proteins and their pleiotropic roles in cardiovascular diseases are discussed, focusing on HF. We also consider the evidence that therapeutic targeting of S100A8/A9 proteins by the humanized vaccine, antibodies, or inhibitors is able to town down inflammatory injuries.