The Loss of Gonadal Hormones Has a Different Impact on Aging Female and Male Mice Submitted to Heart Failure-Inducing Metabolic Hypertensive Stress
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Echocardiography
2.3. Myocardial Fibrosis Evaluation
2.4. Cardiomyocyte Cross-Sectional Area
2.5. RNA Isolation and Quantitative Real-Time Polymerase Chain Reaction
2.6. Western Blots
2.7. Plasma Inflammatory Marker Measurements
2.8. Statistical Analysis
3. Results
3.1. Short and Long-Term Effects on Cardiac Morphology and Function in Male and Female Mice
3.2. Aging in Female Mice Is Associated with a Circulatory Inflammation Profile
3.3. The Effects of Metabolic Hypertensive Stress (MHS) Are Similar in Mice Regardless of Age, Sex, or Gx
3.4. In Young Female Mice, MHS Induced a Circulatory Inflammation Profile Similar to Aging
3.5. Modulation of Myocardial Hypertrophy and Fibrosis Marker Genes by MHS
3.6. MHS Increases the Pyruvate Dehydrogenase Kinase 4 (PDK4) Protein Content in Young and Old HFpEF Male and Female Mice
3.7. Loss of Testosterone Rescues LV Systolic Function in Old MHS Males
4. Discussion
Study Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AngII | Angiotensin II |
HFpEF | Heart failure with preserved ejection fraction |
HFrEF | Heart failure with reduced ejection fraction |
MHS | Metabolic and hypertensive stress (AngII + HFD) |
HFD | High-fat diet |
LA | Left atrial or left atrium |
LV | Left ventricle |
Gx | Gonadectomized |
Ovx | Ovariectomized or ovariectomy |
Ocx | Orchiectomized or orchiectomy |
CH | Cardiac hypertrophy |
EF | Ejection fraction |
FCG | Four core genotypes |
ECM | Extracellular matrix |
EDD | End-diastolic diameter |
ESD | End-systolic diameter |
RWT | Relative wall thickness |
SV | Stroke volume |
CO | Cardiac output |
BW | Body weight |
CSA | Cross-sectional area |
VE | Voluntary exercise |
VCD | Vinylcyclohexene dioxide |
L-NAME | L-NG-Nitroarginine Methyl Ester |
HRT | Hormonal replacement therapy |
EDV | End-diastolic volume |
ESV | End-systolic volume |
Nppa | Atrial natriuretic peptide |
Nppb | Brain natriuretic peptide |
Col1a | Pro-collagen1 alpha |
Col3a | Pro-collagen3 alpha |
Postn | Periostin |
Thbs4 | Thrombospondin 4 |
CD36/FAT | CD36/fatty acid transporter |
Cpt1b | Carnitine palmitoyl transferase 1b |
Glut4 | Glucose transporter 4 |
Pdk4 | Pyruvate dehydrogenase kinase 4 |
PDH | Pyruvate dehydrogenase |
Bdh1 | 3-Hydroxybutyrate Dehydrogenase 1 |
AMPK1b | Adenosyl monophosphate kinase 1b |
GAPDH | Glyceraldehyde 3-phosphate dehydrogenase |
PW | Posterior wall |
IVSW | Interventricular septal wall |
SEM | Standard error of the mean |
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Teou, D.C.; Labbé, E.-A.; Thibodeau, S.-È.; Walsh-Wilkinson, É.; Morin-Grandmont, A.; Trudeau, A.-S.; Arsenault, M.; Couet, J. The Loss of Gonadal Hormones Has a Different Impact on Aging Female and Male Mice Submitted to Heart Failure-Inducing Metabolic Hypertensive Stress. Cells 2025, 14, 870. https://doi.org/10.3390/cells14120870
Teou DC, Labbé E-A, Thibodeau S-È, Walsh-Wilkinson É, Morin-Grandmont A, Trudeau A-S, Arsenault M, Couet J. The Loss of Gonadal Hormones Has a Different Impact on Aging Female and Male Mice Submitted to Heart Failure-Inducing Metabolic Hypertensive Stress. Cells. 2025; 14(12):870. https://doi.org/10.3390/cells14120870
Chicago/Turabian StyleTeou, Diwaba Carmel, Emylie-Ann Labbé, Sara-Ève Thibodeau, Élisabeth Walsh-Wilkinson, Audrey Morin-Grandmont, Ann-Sarah Trudeau, Marie Arsenault, and Jacques Couet. 2025. "The Loss of Gonadal Hormones Has a Different Impact on Aging Female and Male Mice Submitted to Heart Failure-Inducing Metabolic Hypertensive Stress" Cells 14, no. 12: 870. https://doi.org/10.3390/cells14120870
APA StyleTeou, D. C., Labbé, E.-A., Thibodeau, S.-È., Walsh-Wilkinson, É., Morin-Grandmont, A., Trudeau, A.-S., Arsenault, M., & Couet, J. (2025). The Loss of Gonadal Hormones Has a Different Impact on Aging Female and Male Mice Submitted to Heart Failure-Inducing Metabolic Hypertensive Stress. Cells, 14(12), 870. https://doi.org/10.3390/cells14120870