Short-term S100A9 blockade with ABR-238901 significantly improved left ventricular ejection fraction compared with untreated mice by Day 21 post-MI (48% vs. 35%, P=0.002).
Does short-term S100A9 blockade improve cardiac function after myocardial infarction?
Short-term S100A9 blockade inhibits inflammation and improves cardiac function in murine models of MI, suggesting a potential therapeutic strategy to prevent heart failure in ACS patients.
Absolute Event Rate: 48% vs 35%
p-value: p=0.002
AIMS: Neutrophils have both detrimental and beneficial effects in myocardial infarction (MI), but little is known about the underlying pathways. S100A8/A9 is a pro-inflammatory alarmin abundantly expressed in neutrophils that is rapidly released in the myocardium and circulation after myocardial ischaemia. We investigated the role of S100A8/A9 in the innate immune response to MI. METHODS AND RESULTS: In 524 patients with acute coronary syndrome (ACS), we found that high plasma S100A8/A9 at the time of the acute event was associated with lower left ventricular ejection fraction (EF) at 1-year and increased hospitalization for heart failure (HF) during follow-up. In wild-type C57BL/6 mice with MI induced by permanent coronary artery ligation, treatment with the S100A9 blocker ABR-238901 during the inflammatory phase of the immune response inhibited haematopoietic stem cell proliferation and myeloid cell egression from the bone marrow. The treatment reduced the numbers of neutrophils and monocytes/macrophages in the myocardium, promoted an anti-inflammatory environment, and significantly improved cardiac function compared with MI controls. To mimic the clinical scenario, we further confirmed the effects of the treatment in a mouse model of ischaemia/reperfusion. Compared with untreated mice, 3-day ABR-238901 treatment significantly improved left ventricular EF (48% vs. 35%, P = 0.002) and cardiac output (15.7 vs. 11.1 mL/min, P = 0.002) by Day 21 post-MI. CONCLUSION: Short-term S100A9 blockade inhibits inflammation and improves cardiac function in murine models of MI. As an excessive S100A8/A9 release is linked to incident HF, S100A9 blockade might represent a feasible strategy to improve prognosis in ACS patients.
“These findings are a major breakthrough in understanding heart attack-related inflammation and help lay the groundwork for developing ways to regenerate damaged heart tissue. As a scientist and a critical care cardiologist, I have seen time and time again the aftermath of heart attacks. New treatments are needed to help survivors live longer, healthier lives.”
Marinković et al. (Mon,) conducted a other in Acute coronary syndrome (ACS) and myocardial infarction (n=524). S100A9 blocker ABR-238901 vs. Untreated controls was evaluated on Left ventricular ejection fraction (EF) by Day 21 post-MI (p=0.002). Short-term S100A9 blockade with ABR-238901 significantly improved left ventricular ejection fraction compared with untreated mice by Day 21 post-MI (48% vs. 35%, P=0.002).