Author + information
- Received October 19, 2018
- Revision received November 24, 2018
- Accepted November 26, 2018
- Published online April 29, 2019.
- Gregory Aubert, MD, PhDa,∗,
- David Y. Barefield, PhDa,∗,
- Alexis R. Demonbreun, PhDa,∗,
- Mohun Ramratnam, MDb,∗,
- Katherine S. Fallon, BSa,
- James L. Warner, BAa,
- Ann E. Rossi, PhDc,
- Michele Hadhazy, BSa,
- Jonathan C. Makielski, MDb and
- Elizabeth M. McNally, MD, PhDc,∗ ()
- aCenter for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago Illinois
- bDivision of Cardiology, Department of Medicine, University of Wisconsin–Madison, Madison, Wisconsin
- cSection of Cardiology, University of Chicago, Chicago Illinois
- ↵∗Address for correspondence:
Dr. Elizabeth M. McNally, Northwestern University Feinberg School of Medicine, Center for Genetic Medicine, 303 East Superior Street, Lurie 7-123, Chicago, Illinois 60611.
• In the heart, SUR2 couples with a potassium channel to form an adenosine triphosphate–sensitive complex that responds to the energy state of the cell.
• The authors deleted SUR2 in adult cardiomyocytes and found a shift of the heart toward glycolytic metabolism, which is protective under cardiac stress.
• SUR2 was found to complex with glucose transporter type 4, the major glucose transporter.
• Drugs that antagonize the SUR2 receptor may be cardioprotective and useful for managing heart failure.
The adult myocardium relies on oxidative metabolism. In ischemic myocardium, such as the embryonic heart, glycolysis contributes more prominently as a fuel source. The sulfonylurea receptor 2 (SUR2) was previously implicated in the normal myocardial transition from glycolytic to oxidative metabolism that occurs during adaptation to postnatal life. This receptor was now selectively deleted in adult mouse myocardium resulting in protection from ischemia reperfusion injury. SUR2-deleted cardiomyocytes had enhanced glucose uptake, and SUR2 forms a complex with the major glucose transporter. These data identify the SUR2 receptor as a target to shift cardiac metabolism to protect against myocardial injury.
↵∗ Drs. Aubert, Barefield, Demonbreun, and Ramratnam contributed equally to this work and are joint first authors.
Supported by National Institutes of Health Grant No. HL 122109. The funders had no role in determining the experimental design or results interpretation. Dr. McNally has served as a consultant for Exonics, AstraZeneca, and Invitae; and is a founder of Ikaika Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received October 19, 2018.
- Revision received November 24, 2018.
- Accepted November 26, 2018.
- 2019 The Authors