Tissue damage leads to release of pro-inflammatory mediators. Among these, leukotriene C 4 (LTC 4 ) is a powerful, intracellularly induced mediator of inflammation, which requires inside-out transport of LTC 4 . We investigated whether release of LTC 4 via the multidrug resistance related protein 1 (MRP1) induces apoptosis in cardiomyocytes in vitro and in vivo. Methods and results: Incubation of cultured embryonic cardiomyocytes (eCM) with recombined LTC 4 caused enhanced rates of reactive oxygen species (ROS) release measured via L012-luminescence method and apoptosis. Pharmacologic LTC 4 receptor blockade antagonized this effect in vitro. To evaluate the relevance of MRP1 mediated LTC 4 release after myocardial injury in vivo, MRP1 −/− mice and FVB wildtype mice (WT) received cryoinjury of the left ventricle. Fourteen days after injury, left-ventricular ejection fraction (EF), end-diastolic volume (EDV), and akinetic myocardial mass (AMM) were quantified via echocardiography. MRP1 −/− mice demonstrated increased EF (MRP1 −/− : 39±3%, WT: 29±4%) and reduced AMM (MRP1 −/− : 13±2% WT: 16±4%), indicating reduced post-infarction remodeling. Mechanistically, LTC 4 serum concentrations and levels of cellular apoptosis were increased in myocardial cryosections of FVB WT mice as compared to MRP1 −/− mice. To identify key targets for pharmacological inhibition of LTC 4 actions, WT mice were treated with the specific Cys-LT1-receptor blocker Montelukast or the MRP1-Inhibitor MK571. Treatment of WT mice resulted in significant increase of EF (WT Montelukast : 40±5%, WT MK571 : 39±3%, WT vehicle : 33±3% and decrease of AMM (WT Montelukast : 12±1%, WT MK571 : 10±3%, WT vehicle : 15±5%) compared to untreated WT mice. Conclusion: Inhibition of leukotriene C 4 reduces levels of oxidative stress and apoptosis and demonstrates beneficial effects on myocardial remodeling after left ventricular injury.