Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction
Open accessAbstract
Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.
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Knockout of AR results in the down-regulation of PGC-1α and TFAM in the muscle of castrated rats and mice, while the administration of exogenous androgen reversed these effects.
“It has been reported that knockout of AR results in the down-regulation of PGC-1α and TFAM in the muscle of castrated rats and mice, while the administration of exogenous androgen reversed these effects (144, 145).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [144]
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- Authors
- Wang, F., Yang, J., Sun, J., Dong, Y., Zhao, H., Shi, H., & Fu, L.
- Affiliations
- Harbin Medical University (CN)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2015-03-13
- Volume
- 225
- Issue
- 2
- Pages
- 101-111
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2103911029
- Cited by
- 41
- References
- 40
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 9 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Education, Heilongjiang Province
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- testosterone replacement therapy, myocardial infarction, mitochondrial dysfunction, mitochondrial dynamics, mitochondrial fission and fusion, castration, PGC-1α, AMPK, mitofusin 2, Drp1, cardiomyocyte apoptosis, myocardial fibrosis, myocarditis, cardiac function, ATP levels
- MeSH terms
- Adenosine Triphosphate, Animals, Disease Models, Animal, Humans, Male, Mitochondria, Myocardial Infarction, Testosterone, Rats, Wistar, Apoptosis, Hormone Replacement Therapy, Myocytes, Cardiac, PPAR gamma, Rats, AMP-Activated Protein Kinases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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