High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
Abstract
:1. Introduction
2. Results
2.1. Mice Body Weight, Glucose, and Plasma Lipids
2.2. ECG Recording
2.3. Echocardiographic Measurements
2.4. Single RyR2 Channel Activity from Mouse Ventricular Muscle
2.5. RyR2 Content and Phosphorylation
2.6. Effect of HFD on the Free Thiol Content of RyR2
2.7. NOX Isoforms in the Hearts of HFD-Fed Mice
3. Discussion
4. Materials and Methods
4.1. Ethical Approval
4.2. Animals and Dietary Model
4.3. Surface Electrocardiogram (ECG)
4.4. Echocardiographic Determinations
4.5. Preparation of Cardiac Subcellular Fractions
4.6. Channel Recording and Analysis
4.7. Western Blot Analysis
4.8. Determination of RyR2 Free Thiol Content
4.9. RNA Isolation and qRT-PCR
- RyR2 forward 5′-CTGAGAACTGATGATGAGGTGGT-3′;
- RyR2 reverse 5′-ATCCTTCTGCTGCCAAGCAC-3′;
- 18S forward 5′CGGACAGGATTGACAGATTG-3′;
- 18S reverse 5′-CAAATCGCTCCACCAACTAA-3′;
- NOX4 forward 5′-TGGCCAACGAAGGGGTTAAA-3′;
- NOX4 reverse 5′-ATGAGGCTGCAGTTGAGGTT-3′;
- NOX2 forward 5′-CTCAGGCCAATCACTTTGCT-3′;
- NOX2 reverse 5′-TTCAGGGCCACACAGGAAAA-3′.
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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n | Control 10 | HFD 10 | Control with Apocynin 8 | HFD with Apocynin 8 |
---|---|---|---|---|
Heart rate (BPM) | 668 ± 113 | 778 ± 142 * | 637 ± 83 | 745 ± 70 * |
LVID diastole, mm | 1.58 ± 0.27 | 1.66 ± 0.58 | 1.74 ± 0.17 | 1.74 ± 0.34 |
LVID systole, mm | 0.78 ± 0.17 | 0.77 ± 0.32 | 0.90 ± 0.18 | 0.96 ± 0.30 |
FS % | 49 ± 12 | 50 ± 16 | 47 ± 14 | 51 ± 11 |
Channel Activity | Ka (µM) | nHill | Ki (µM) |
---|---|---|---|
Low | 47 ± 16 | 1.5 # | 7.0 ± 2.4 |
Moderate | 9.3 ± 1.7 * | 1 # | 177 ± 28 $ |
High | 1.1 ± 0.1 *,$ | 3 # | 5000 # |
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Sánchez, G.; Araneda, F.; Peña, J.P.; Finkelstein, J.P.; Riquelme, J.A.; Montecinos, L.; Barrientos, G.; Llanos, P.; Pedrozo, Z.; Said, M.; et al. High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice. Int. J. Mol. Sci. 2018, 19, 533. https://doi.org/10.3390/ijms19020533
Sánchez G, Araneda F, Peña JP, Finkelstein JP, Riquelme JA, Montecinos L, Barrientos G, Llanos P, Pedrozo Z, Said M, et al. High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice. International Journal of Molecular Sciences. 2018; 19(2):533. https://doi.org/10.3390/ijms19020533
Chicago/Turabian StyleSánchez, Gina, Felipe Araneda, Juan Pedro Peña, José Pablo Finkelstein, Jaime A. Riquelme, Luis Montecinos, Genaro Barrientos, Paola Llanos, Zully Pedrozo, Matilde Said, and et al. 2018. "High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice" International Journal of Molecular Sciences 19, no. 2: 533. https://doi.org/10.3390/ijms19020533