Myeloperoxidase Inhibition Improves Ventricular Function and Remodeling After Experimental Myocardial Infarction

JACC Basic Transl Sci. 2016 Dec 26;1(7):633-643. doi: 10.1016/j.jacbts.2016.09.004. eCollection 2016 Dec.


PF-1355 is an oral myeloperoxidase (MPO) inhibitor that successfully decreased elevated MPO activity in mouse myocardial infarction models. Short duration PF-1355 treatment for 7 days decreased the number of inflammatory cells and attenuated left ventricular dilation. Cardiac function and remodeling improved when treatment was increased to 21 days. Better therapeutic effect was further achieved with early compared with delayed treatment initiation (1 h vs. 24 h after infarction). In conclusion, PF-1355 treatment protected a mouse heart from acute and chronic effects of MI, and this study paves the way for future translational studies investigating this class of drugs in cardiovascular diseases.

Keywords: CNR, contrast to noise ratio; EDV, end-diastolic volume; EF, ejection fraction; IRI, ischemia reperfusion injury; LAR, lesion activation ratio; Ly-6C, lymphocyte antigen 6C; MI, myocardial infarction; MPO, myeloperoxidase; MPO-Gd, bis-5-hydroxytryptamide-diethylenetriaminepentaacetate-gadolinium; MPO−/−, myeloperoxidase knock out; inflammation; myeloperoxidase; myocardial infarction; oxidative stress; treatment.

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