JACC: Basic to Translational Science (Jun 2019)
Malonyl CoA Decarboxylase Inhibition Improves Cardiac Function Post-Myocardial Infarction
- Wei Wang, MD, PhD,
- Liyan Zhang, PhD,
- Pavan K. Battiprolu, PhD,
- Arata Fukushima, MD, PhD,
- Khanh Nguyen, BS,
- Kenneth Milner, BS,
- Abhishek Gupta, PhD,
- Tariq Altamimi, PhD,
- Nikole Byrne, BS,
- Jun Mori, MD, PhD,
- Osama Abo Alrob, PhD,
- Cory Wagg,
- Natasha Fillmore, PhD,
- Shao-hua Wang, MD, PhD,
- Dongming M. Liu, BS,
- Angela Fu, BS,
- Jenny Yinglin Lu, BS,
- Mary Chaves, MS,
- Alykhan Motani, PhD,
- John R. Ussher, PhD,
- Jeff D. Reagan, PhD,
- Jason R.B. Dyck, PhD,
- Gary D. Lopaschuk, PhD
Affiliations
- Wei Wang, MD, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Cardiac Surgery, University of Alberta, Edmonton, Alberta, Canada
- Liyan Zhang, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Pavan K. Battiprolu, PhD
- Amgen, San Francisco, California
- Arata Fukushima, MD, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Khanh Nguyen, BS
- Amgen, San Francisco, California
- Kenneth Milner, BS
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Abhishek Gupta, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Tariq Altamimi, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Nikole Byrne, BS
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Jun Mori, MD, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Osama Abo Alrob, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Cory Wagg
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Natasha Fillmore, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Shao-hua Wang, MD, PhD
- Department of Cardiac Surgery, University of Alberta, Edmonton, Alberta, Canada
- Dongming M. Liu, BS
- Amgen, San Francisco, California
- Angela Fu, BS
- Amgen, San Francisco, California
- Jenny Yinglin Lu, BS
- Amgen, San Francisco, California
- Mary Chaves, MS
- Amgen, San Francisco, California
- Alykhan Motani, PhD
- Amgen, San Francisco, California
- John R. Ussher, PhD
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
- Jeff D. Reagan, PhD
- Amgen, San Francisco, California
- Jason R.B. Dyck, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Gary D. Lopaschuk, PhD
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Address for correspondence: Dr. Gary Lopaschuk, Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, 423 Heritage Medical Research Center, University of Alberta, Edmonton T6G 2S2, Canada.
- Journal volume & issue
-
Vol. 4,
no. 3
pp. 385 – 400
Abstract
Summary: Alterations in cardiac energy metabolism after a myocardial infarction contribute to the severity of heart failure (HF). Although fatty acid oxidation can be impaired in HF, it is unclear if stimulating fatty acid oxidation is a desirable approach to treat HF. Both immediate and chronic malonyl coenzyme A decarboxylase inhibition, which decreases fatty acid oxidation, improved cardiac function through enhancing cardiac efficiency in a post–myocardial infarction rat that underwent permanent left anterior descending coronary artery ligation. The beneficial effects of MCD inhibition were attributed to a decrease in proton production due to an improved coupling between glycolysis and glucose oxidation. Key Words: fatty acid oxidation, heart failure, glucose oxidation, uncoupling of glycolysis
