| المؤلفون: |
Mouton AJ; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., Aitken NM; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., Morato JG; University of Mississippi Medical Center, Jackson, MS, United States., do Carmo JM; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., da Silva AA; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., Omoto AC; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., Li X; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., Wang Z; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States., Schrimpe-Rutledge AC; Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, United States., Codreanu SG; Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, United States., Sherrod SD; Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, United States., McLean JA; Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, United States., Stanford JK; Medicine, University of Mississippi Medical Center, Jackson, MS, United States., Brown JA; Jackson State University, Jackson, MS, United States., Hall JE; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States. |
| مستخلص: |
Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism. |
