JACC: Basic to Translational Science (Dec 2016)
Myeloperoxidase Inhibition Improves Ventricular Function and Remodeling After Experimental Myocardial Infarction
- Muhammad Ali, MD,
- Benjamin Pulli, MD,
- Gabriel Courties, PhD,
- Benoit Tricot, MSc,
- Matthew Sebas, BSc,
- Yoshiko Iwamoto, BSc,
- Ingo Hilgendorf, MD,
- Stefan Schob, MD,
- Anping Dong, MD, PhD,
- Wei Zheng, MD,
- Athanasia Skoura, PhD,
- Amit Kalgukar, PhD,
- Christian Cortes, MSc,
- Roger Ruggeri, PhD,
- Filip K. Swirski, PhD,
- Matthias Nahrendorf, MD, PhD,
- Leonard Buckbinder, PhD,
- John W. Chen, MD, PhD
Affiliations
- Muhammad Ali, MD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Benjamin Pulli, MD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Gabriel Courties, PhD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Benoit Tricot, MSc
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Matthew Sebas, BSc
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Yoshiko Iwamoto, BSc
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Ingo Hilgendorf, MD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Stefan Schob, MD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Anping Dong, MD, PhD
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- Wei Zheng, MD
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- Athanasia Skoura, PhD
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- Amit Kalgukar, PhD
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- Christian Cortes, MSc
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- Roger Ruggeri, PhD
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- Filip K. Swirski, PhD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Matthias Nahrendorf, MD, PhD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Leonard Buckbinder, PhD
- Pfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- John W. Chen, MD, PhD
- Center for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- DOI
- https://doi.org/10.1016/j.jacbts.2016.09.004
- Journal volume & issue
-
Vol. 1,
no. 7
pp. 633 – 643
Abstract
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
