Myeloperoxidase Inhibition Improves Ventricular Function and Remodeling After Experimental Myocardial Infarction

Highlights •The inflammatory enzyme MPO is a potential therapeutic target in cardiovascular diseases. •PF-1355 is an orally bioavailable mechanism-based inhibitor of MPO enzymatic activity. PF-1355 treatment successfully inhibited MPO in mouse models of myocardial infarction and ischemia reperfusion injury. •Short duration oral drug treatment for 7 days attenuated inflammation and cardiac dilation during early infarct healing. However, MPO-containing cells persisted beyond 7 days. •Prolonged 21-day treatment improved ejection fraction (∼44%) and decreased end-diastolic volume (∼53%) and left ventricular mass (∼33%) compared with untreated control subjects. •Better therapeutic effect was also achieved when treatment was started early (at 1 h) after the initial ischemic insult.