Attenuation of Adverse Postinfarction Left Ventricular Remodeling with Empagliflozin Enhances Mitochondria-Linked Cellular Energetics and Mitochondrial Biogenesis
Abstract
:1. Introduction
2. Results
2.1. The Effect of EMPA on Postinfarction Adverse LV Remodeling in WT Mice and Immune Cell Infiltration
2.2. The Effect of EMPA on Mitochondrial Energetics and Content in H9C2 Cardiac Cells
2.3. Effect of EMPA on Postinfarction Adverse LV Remodeling and Immune Cell Infiltration in Mitophagy-Impaired PKO Mice
2.4. The Effect of EMPA on Isolated Mitochondria Obtained from WT Mice and PKO Mice with Impaired Mitophagy
3. Materials and Methods
3.1. Animals
3.2. Animal Protocol for In Vivo Wild-Type and PKO Mouse Studies
3.3. Echocardiography
3.4. Histology for Immune Cell Infiltration and Fibrosis Post-MI
3.5. Effect of EMPA on Mitophagy and Mitochondrial Biogenesis on Differentiated H9C2 Cells
3.6. Subcellular Fractionation of Heart Tissues and Differentiated H9C2 Cells
3.7. Western Blot Analysis
3.8. Seahorse Mitochondria Stress Test (Respirometry)
3.9. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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14 Day | 28 Day | |||||
---|---|---|---|---|---|---|
WT-VEH(7) | WT-EMPA(8) | p Value | WT-VEH(6) | WT-EMPA(7) | p Value | |
HR (bpm) | 451 ± 70.48 | 429 ± 49.65 | 0.49 | 440 ± 71.57 | 397 ± 35.10 | 0.19 |
EF (%) | 38.71 ± 5.76 | 50.42 ± 8.34 | 0.01 | 34.40 ± 8.32 | 47.85 ± 11.16 | 0.03 |
FS (%) | 18.70 ± 3.02 | 25.74 ± 5.21 | 0.01 | 16.51 ± 4.37 | 24.26 ± 6.53 | 0.03 |
LV Mass (mg) | 152.52 ± 21.22 | 156.42 ± 57.44 | 0.87 | 136.15 ± 34.31 | 127.01 ± 32.33 | 0.63 |
LV Mass (Corrected) (mg) | 122.02 ± 16.98 | 125.13 ± 45.95 | 0.87 | 136.15 ± 34.31 | 127.01 ± 32.33 | 0.63 |
LV Vol; d (μL) | 93.87 ± 14.75 | 97.00 ± 25.34 | 0.78 | 119.96 ± 61.41 | 100.99 ± 36.56 | 0.51 |
LV Vol; s (μL) | 58.18 ± 14.61 | 48.65 ± 17.09 | 0.27 | 81.43 ± 51.59 | 54.54 ± 26.76 | 0.25 |
LVID; d (mm) | 4.52 ± 0.30 | 4.57 ± 0.48 | 0.83 | 4.93 ± 0.97 | 4.61 ± 0.72 | 0.51 |
LVID; s (mm) | 3.68 ± 0.38 | 3.40 ± 0.48 | 0.23 | 4.14 ± 0.99 | 3.52 ± 0.75 | 0.22 |
LVPW; d (mm) | 0.92 ± 0.10 | 0.88 ± 0.13 | 0.54 | 0.86 ± 0.20 | 0.95 ± 0.18 | 0.41 |
LVPW; s (mm) | 1.01 ± 0.12 | 1.15 ± 0.14 | 0.05 | 1.01 ± 0.21 | 1.20 ± 0.17 | 0.10 |
PKO-VEH(7) | PKO-EMPA(9) | p Value | |
---|---|---|---|
HR (bpm) | 410 ± 35.29 | 385 ± 12.65 | 0.24 |
EF (%) | 36.28 ± 7.75 | 46.58 ± 10.78 | 0.04 |
FS (%) | 17.70 ± 7.75 | 23.44 ± 6.34 | 0.05 |
LV Mass (mg) | 144.52 ± 39.27 | 145.2 ± 42.29 | 0.60 |
LV Mass (Corrected) (mg) | 115.62 ± 31.42 | 116.16 ± 33.83 | 0.60 |
LV Vol; d (μL) | 98.53 ± 35.39 | 99.04 ± 39.54 | 0.60 |
LV Vol; s (μL) | 64.84 ± 27.38 | 56.23 ± 33.19 | 0.29 |
LVID; d (mm) | 4.56 ± 0.74 | 4.57 ± 0.75 | 0.56 |
LVID; s (mm) | 3.78 ± 0.80 | 3.54 ± 0.86 | 0.26 |
LVPW; d (mm) | 0.83 ± 0.27 | 0.79 ± 0.17 | 0.63 |
LVPW; s (mm) | 1.04 ± 0.27 | 1.08 ± 0.26 | 0.77 |
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Song, Y.; Huang, C.; Sin, J.; Germano, J.d.F.; Taylor, D.J.R.; Thakur, R.; Gottlieb, R.A.; Mentzer, R.M., Jr.; Andres, A.M. Attenuation of Adverse Postinfarction Left Ventricular Remodeling with Empagliflozin Enhances Mitochondria-Linked Cellular Energetics and Mitochondrial Biogenesis. Int. J. Mol. Sci. 2022, 23, 437. https://doi.org/10.3390/ijms23010437
Song Y, Huang C, Sin J, Germano JdF, Taylor DJR, Thakur R, Gottlieb RA, Mentzer RM Jr., Andres AM. Attenuation of Adverse Postinfarction Left Ventricular Remodeling with Empagliflozin Enhances Mitochondria-Linked Cellular Energetics and Mitochondrial Biogenesis. International Journal of Molecular Sciences. 2022; 23(1):437. https://doi.org/10.3390/ijms23010437
Chicago/Turabian StyleSong, Yang, Chengqun Huang, Jon Sin, Juliana de F. Germano, David J. R. Taylor, Reetu Thakur, Roberta A. Gottlieb, Robert M. Mentzer, Jr., and Allen M. Andres. 2022. "Attenuation of Adverse Postinfarction Left Ventricular Remodeling with Empagliflozin Enhances Mitochondria-Linked Cellular Energetics and Mitochondrial Biogenesis" International Journal of Molecular Sciences 23, no. 1: 437. https://doi.org/10.3390/ijms23010437