Background: Plasma levels of the polymorphonuclear neutrophil (PMN)-derived enzyme myeloperoxidase (MPO) correlate with prognosis and severity of myocardial infarction (MI). Apart from its capacity to catalyse the generation of highly reactive oxygen specy (ROS) hydrogen peroxide (H₂O₂), MPO attracts and activates PMN and monocytes, cells playing a crucial role in inflammation and tissue remodelling post MI.

Purpose: Herein we evaluate the role of MPO on monocyte and macrophage activation in vitro and ex vivo, and extrapolate this using a murine model of MI.

Methods and Results: THP-1 monocytes incubated overnight with MPO (10ng/ml) in the presence H2O2 showed increased chemokine receptor CCR2 as compared to unstimulated cells. In vivo, intraperitoneal injection of MPO (15 µg) in Mpo^-/- mice resulted in a marked increase in peritoneal leukocyte recruitment compared to mice injected with saline. These leukocytes were subsequently identified as macrophages (F4/80⁺) by flow cytometry. Using a murine MI model of permanent ligation of the left descending coronary artery (LAD) we showed a reduced macrophage infiltration in the infarct- and peri-infarct area in Mpo^-/- mice as compared to WT animals after three days. Furthermore, splenic monocyte mobilisation was significantly decreased in Mpo^-/- mice as early as one day after LAD ligation suggesting a role for MPO in monocyte/macrophage recruitment in MI.

Conclusions: Herein we identify MPO as a mediator of monocyte and macrophage recruitment and activation after myocardial infarction. Impacting plasma MPO levels may offer a therapeutic target to modulate tissue remodelling post MI.