Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids
Abstract
:1. Introduction
2. Results
2.1. Cardiac Na+/K+-ATPase in the α1s/sα2s/s Mouse
2.2. Cardiac Phenotype of the α1s/sα2s/s Mouse
2.3. Absence of Adverse Cardiac Remodeling in α1s/sα2s/s Mice
2.4. RNA-Seq Analysis
2.5. Evidence of Activation of the Na/K-ATPase Oxidant Amplification Loop in α1s/sα2s/s Mice
2.6. Angiotensin-II Does Not Induce Cardiac Fibrosis in α1s/sα2s/s Mice
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Generation of the NKA α1 Sensitive Mouse Model
4.3. Western Blot Analysis
4.4. Na/K-ATPase Activity and Ouabain Dose-Response in Heart Lysates
4.5. Echocardiography
4.6. Histology
4.7. Determination of mRNA Levels
4.8. Angiotensin-II Treatment
4.9. RNA Sequencing (RNA-Seq) Analysis
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | α1r/rα2s/s (n = 9) | α1s/sα2s/s (n = 6) |
---|---|---|
HR (bpm) | 457 ± 23 | 475 ± 31 |
LVID; s (mm) | 2.50 ± 0.52 | 2.60 ± 0.42 |
LVID; d (mm) | 3.61 ± 0.54 | 3.86 ± 0.28 |
LV Volume; s (µL) | 23.7 ± 10.6 | 25.5 ± 9.2 |
LV Volume; d (µL) | 56.6 ± 18.7 | 64.9 ± 11.0 |
SV (µL) | 32.9 ± 11.2 | 39.4 ± 3.8 |
EF (%) | 59 ± 11 | 62 ± 9 |
FS (%) | 31 ± 7 | 33 ± 7 |
CO (mL/min) | 14.9 ± 4.7 | 18.7 ± 2.1 |
LVAW; s (mm) | 1.34 ± 0.16 | 1.53 ± 0.12 * |
LVAW; d (mm) | 0.95 ± 0.12 | 1.06 ± 0.11 |
LVPW; s (mm) | 1.19 ± 0.17 | 1.24 ± 0.24 |
LVPW; d (mm) | 0.80 ± 0.10 | 0.84 ± 0.18 |
LV Mass (mg) | 87.1 ± 12.4 | 110.7 ± 19.9 * |
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Marck, P.V.; Pessoa, M.T.; Xu, Y.; Kutz, L.C.; Collins, D.M.; Yan, Y.; King, C.; Wang, X.; Duan, Q.; Cai, L.; et al. Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids. Int. J. Mol. Sci. 2021, 22, 3462. https://doi.org/10.3390/ijms22073462
Marck PV, Pessoa MT, Xu Y, Kutz LC, Collins DM, Yan Y, King C, Wang X, Duan Q, Cai L, et al. Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids. International Journal of Molecular Sciences. 2021; 22(7):3462. https://doi.org/10.3390/ijms22073462
Chicago/Turabian StyleMarck, Pauline V., Marco T. Pessoa, Yunhui Xu, Laura C. Kutz, Dominic M. Collins, Yanling Yan, Cierra King, Xiaoliang Wang, Qiming Duan, Liquan Cai, and et al. 2021. "Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids" International Journal of Molecular Sciences 22, no. 7: 3462. https://doi.org/10.3390/ijms22073462