Pyridoxamine Alleviates Cardiac Fibrosis and Oxidative Stress in Western Diet-Induced Prediabetic Rats
Abstract
:1. Introduction
2. Results
2.1. Pyridoxamine Improves Fasting Blood Glucose Levels in Western Diet-Fed Rats
2.2. Pyridoxamine Tends to Prevent Western Diet-Induced LV Dilation
2.3. Pyridoxamine Limits LV Fibrosis and Oxidative Stress in Western Diet-Fed Rats
3. Discussion
3.1. A Translatable Rat Model of Diet-Induced Diabetic Cardiomyopathy
3.2. PM as a Potential Cardioprotective Strategy in T2DM Development
3.3. Safety and Efficacy of PM
3.4. Limitations
4. Materials and Methods
4.1. Animal Model and Study Design
4.2. Oral Glucose Tolerance Test and Insulin Measurements
4.3. Conventional Echocardiographic Measurements
4.4. Hemodynamic Measurements
4.5. Histology
4.6. Immunohistochemistry
4.7. RT-qPCR
4.8. Plasma Advanced Glycation End Products Determination
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
4-HNE | 4-hydroxynenonal |
Ad | Diastolic area |
AGEs | Advanced glycation end products |
As | Systolic area |
AUC | Area under the curve |
AWTd | Anterior wall thickness in diastole |
AWTs | Anterior wall thickness in systole |
BSA | Body surface area |
CO | Cardiac output |
CSA | Cross-sectional cardiomyocyte area |
CVD | Cardiovascular diseases |
DCM | Diabetic cardiomyopathy |
E/A | Ratio of peak mitral flow velocity in early versus late filling |
E’ | Peak septal mitral annulus velocity in the early filling phase |
E/E’ | Ratio of peak mitral flow velocity versus peak mitral annular velocity |
EDP | End-diastolic pressure |
EDV | End-diastolic volume |
EF | Ejection fraction |
ESP | End-systolic pressure |
ESV | End-systolic volume |
FS | Fractional shortening |
GPx1 | Glutathione peroxidase 1 |
H&E | Hematoxylin and eosin |
HFD | High-fat diet |
HFpEF | Heart failure with a preserved ejection fraction |
HFrEF | Heart failure with reduced ejection fraction |
HOMA-IR | Homeostatic model assessment for insulin resistance |
HPRT | Hypoxanthine-guanine phosphoribosyl transferase |
HR | Heart rate |
i.p. | Intraperitoneally |
IDd | Internal diameter in diastole |
IDs | Internal diameter in systole |
IVSd | Interventricular septum thickness in diastole |
IVSs | Interventricular septum thickness in systole |
LV | Left ventricular |
NOX4 | Nicotinamide adenine dinucleotide phosphate oxidase 4 |
OGTT | Oral glucose tolerance test |
PGK1 | Phosphoglycerate kinase 1 |
PM | Pyridoxamine |
PWTd | Posterior wall thickness in diastole |
PWTs | Posterior wall thickness in systole |
RAGE | Receptor for advanced glycation end products |
RCS | Reactive carbonyl species |
ROS | Reactive oxygen species |
RT | Room temperature |
RT-qPCR | Real-Time quantitative polymerase chain reaction |
SEM | Standard error of the mean |
SOD2 | Superoxide dismutase |
SV | Stroke volume |
T2DM | Type 2 diabetes mellitus |
Tau | Time constant for isovolumetric relaxation |
WD | Western diet |
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CD | WD | WD + PM | |
---|---|---|---|
EDV/BSA (µL/cm2) | 0.841 ± 0.046 | 1.037 ± 0.104 | 0.866 ± 0.043 |
ESV/BSA (µL/cm2) | 0.196 ± 0.027 | 0.327 ± 0.028 * | 0.232 ± 0.028 |
Ad/BSA (mm2/cm2) | 0.149 ± 0.007 | 0.157 ± 0.009 | 0.144 ± 0.005 |
As/BSA (mm2/cm2) | 0.062 ± 0.005 | 0.081 ± 0.002 * | 0.063 ± 0.005 |
EF (%) | 78 ± 2 | 68 ± 3 | 73 ± 3 |
HR (bpm) | 326 ± 15 | 340 ± 10 | 341 ± 10 |
BSA (cm2) | 739 ± 10 | 822 ± 24 * | 811 ± 14 ** |
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D’Haese, S.; Claes, L.; Jaeken, E.; Deluyker, D.; Evens, L.; Heeren, E.; Haesen, S.; Vastmans, L.; Lambrichts, I.; Wouters, K.; et al. Pyridoxamine Alleviates Cardiac Fibrosis and Oxidative Stress in Western Diet-Induced Prediabetic Rats. Int. J. Mol. Sci. 2024, 25, 8508. https://doi.org/10.3390/ijms25158508
D’Haese S, Claes L, Jaeken E, Deluyker D, Evens L, Heeren E, Haesen S, Vastmans L, Lambrichts I, Wouters K, et al. Pyridoxamine Alleviates Cardiac Fibrosis and Oxidative Stress in Western Diet-Induced Prediabetic Rats. International Journal of Molecular Sciences. 2024; 25(15):8508. https://doi.org/10.3390/ijms25158508
Chicago/Turabian StyleD’Haese, Sarah, Lisa Claes, Eva Jaeken, Dorien Deluyker, Lize Evens, Ellen Heeren, Sibren Haesen, Lotte Vastmans, Ivo Lambrichts, Kristiaan Wouters, and et al. 2024. "Pyridoxamine Alleviates Cardiac Fibrosis and Oxidative Stress in Western Diet-Induced Prediabetic Rats" International Journal of Molecular Sciences 25, no. 15: 8508. https://doi.org/10.3390/ijms25158508