Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Wang, Fengyue; Yang, Jing; Sun, Jing; Dong, Yanli; Zhao, Hong; Shi, Hui; Fu, Lu

doi:10.1530/joe-14-0638

Cited by 36 publications

(41 citation statements)

References 41 publications

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“…These results suggested that testosterone could enhance fatty acid metabolism to increase ATP generation for the ischemic heart by upregulating PPAR α . We have demonstrated that testosterone could protect mitochondria in the postinfarct myocardium and attenuates a decrease in ATP levels and cardiomyocyte apoptosis [ 24 ]. In line with our findings, chronic activation of PPAR α upregulates the fatty acid metabolic pathway despite the accumulation of myocardial triglycerides without worsening left ventricular dysfunction in a rat infarct model of heart failure [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…The above-mentioned studies indicated that testosterone could modulate PPAR α expression through AR-independent mechanism. We have proved that testosterone can partly via the AMP-activated protein kinase- (AMPK-) peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1 α ) pathway protect against mitochondrial dysfunction and cardiomyocyte apoptosis in the postinfarct myocardium [ 24 ]. PGC-1 α can bind to the heterodimers formed by PPAR α and retinoic acid-activated receptor (RXR) and then coactivate PPAR α to enhance fatty acid utilization in myocardium [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Serum testosterone and 17 β -estradiol levels were measured with commercially available enzyme-linked immunoassay (ELISA) kits (Uscn Life Science, Inc., Houston, TX, USA). All procedures were performed according to the manual as previously described [ 24 ]. The limit of detection was 0.0437 ng/mL for testosterone and 4.75 pg/mL for 17 β -estradiol.…”

Section: Methodsmentioning

confidence: 99%

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Testosterone Replacement Modulates Cardiac Metabolic Remodeling after Myocardial Infarction by Upregulating PPARα

et al. 2016

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Despite the importance of testosterone as a metabolic hormone, its effects on myocardial metabolism in the ischemic heart remain unclear. Myocardial ischemia leads to metabolic remodeling, ultimately resulting in ATP deficiency and cardiac dysfunction. In the present study, the effects of testosterone replacement on the ischemic heart were assessed in a castrated rat myocardial infarction model established by ligating the left anterior descending coronary artery 2 weeks after castration. The results of real-time PCR and Western blot analyses showed that peroxisome proliferator-activated receptor α (PPARα) decreased in the ischemic myocardium of castrated rats, compared with the sham-castration group, and the mRNA expression of genes involved in fatty acid metabolism (the fatty acid translocase CD36, carnitine palmitoyltransferase I, and medium-chain acyl-CoA dehydrogenase) and glucose transporter-4 also decreased. A decline in ATP levels in the castrated rats was accompanied by increased cardiomyocyte apoptosis and fibrosis and impaired cardiac function, compared with the sham-castration group, and these detrimental effects were reversed by testosterone replacement. Taken together, our findings suggest that testosterone can modulate myocardial metabolic remodeling by upregulating PPARα after myocardial infarction, exerting a protective effect on cardiac function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Testosterone Replacement Modulates Cardiac Metabolic Remodeling after Myocardial Infarction by Upregulating PPARα

et al. 2016

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“…Previous reports suggested that these adverse cardiac effects are due to mitochondrial dysfunction [4, 6]. Mitochondria are highly mobile organelles, and their function is controlled by mitochondrial dynamics [7, 8]. Changes in the fission/fusion balance in mitochondria can lead to mitochondrial dysfunction and apoptosis [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Testosterone Deprivation Aggravates Left-Ventricular Dysfunction in Male Obese Insulin-Resistant Rats via Impairing Cardiac Mitochondrial Function and Dynamics Proteins

et al. 2018

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Background: We have previously reported that testosterone deprivation at a very young age accelerated, but did not aggravate, left-ventricular (LV) dysfunction in obese insulin-resistant rats. However, the effects of testosterone deprivation during adulthood on LV function in obese insulin-resistant rats remains unclear. We hypothesized that testosterone deprivation aggravates LV dysfunction and cardiac autonomic imbalance via the impairment of cardiac mitochondrial function and dynamics proteins, a reduction in insulin receptor function, and an increase in apoptosis in obese insulin-resistant rats. Methods: Male rats were fed on either a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. They were then subdivided into 2 groups: sham operation (NDS, HFS) and orchiectomy (NDO, HFO). Metabolic parameters, blood pressure, heart rate variability (HRV), and LV function were determined at baseline and before and after orchiectomy. Mitochondrial function and dynamics proteins, insulin signaling, and apoptosis were determined 12 weeks postoperatively. Results: HFS rats exhibited obese insulin resistance, depressed HRV, and LV dysfunction. In HFO rats, systolic blood pressure was increased with more excessive depression of HRV and increased LV dysfunction, compared with HFS rats. These adverse cardiac effects were consistent with markedly increased mitochondrial dysfunction, reduced mitochondrial complex I and III proteins, reduced mitochondrial fusion proteins, and increased apoptosis, compared with HFS rats. However, testosterone deprivation did not lead to any alteration in the insulin-resistant condition in HFO rats, compared with HFS rats. Conclusion: We concluded that testosterone deprivation during adulthood aggravated the impairment of mitochondrial function, mitochondrial respiratory complex, mitochondrial dynamics proteins, and apoptosis, leading to LV dysfunction in obese insulin-resistant rats.

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“…A close association has been identified between altered mitochondrial morphology and dynamics and MI injury [5]. It has also been reported that the protection of mitochondria in the post-infarct myocardium resulted in decreased mitochondrial dysfunction and cardiomyocyte apoptosis [6]. In addition, oxidative stress occurred mainly in the mitochondria; damaged cells attack the mitochondria [7].…”

Section: Introductionmentioning

confidence: 99%

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis

Tian

Yang

et al. 2017

J Biomed Sci

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BackgroundMyocardial infarction (MI) is an acute and fatal condition that threatens human health. Dl-3-n-butylphthalide (NBP) has been used for the treatment of acute ischemic stroke. Mitochondria may play a protective role in MI injury. However, there are few reports on the cardioprotective effect of NBP or the potential mitochondrial mechanism for the NBP-induced protection against cardiac ischemia injury. We investigated the therapeutic effects of NBP in an in vivo MI model and an in vitro oxidative stress model, as well as the potential mitochondrial mechanism.MethodsThis study comprised two different experiments. The aim of experiment 1 was to determine the protective effects of NBP on MI and the underlying mechanisms in vivo. In part 1, myocardial infarct size was measured by staining with 2,3,5-triphenyltetrazoliumchloride (TTC). Myocardial enzymes and mitochondrial enzymes were assayed. The aim of experiment 2 was to investigate the role of NBP in H2O2-induced myocardial ischemic injury in H9c2 cells and to determine the potential mechanism. In part 2, H9c2 cell viability was evaluated. ROS levels, mitochondrial morphology, and mitochondrial membrane potential of H9c2 cells were measured. ATP levels were evaluated using an assay kit; mitochondrial DNA (mtDNA), the expressions of NRF-1 and TFAM, and mitochondrial biogenesis factors were determined.ResultsNBP treatment significantly reduced the infarct ratio, as observed by TTC staining, decreased serum myocardial enzymes in MI, and restored heart mitochondrial enzymes (isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and a-ketoglutarate dehydrogenase (a-KGDH) activities after MI. Moreover, in in vitro studies, NBP significantly increased the viability of H9c2 cells in a dose-dependent manner, reduced cell apoptosis, protected mitochondrial functions, elevated the cellular ATP levels, and promoted H2O2-induced mitochondrial biogenesis in H9c2 cardiomyoblasts.ConclusionCollectively, the results from both the in vivo and in vitro experiments suggested that NBP exerted a cardioprotective effect on cardiac ischemic injury via the regulation of mitochondrial function and biogenesis.

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Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Cited by 36 publications

References 41 publications

Testosterone Replacement Modulates Cardiac Metabolic Remodeling after Myocardial Infarction by Upregulating PPARα

Testosterone Replacement Modulates Cardiac Metabolic Remodeling after Myocardial Infarction by Upregulating PPARα

Testosterone Deprivation Aggravates Left-Ventricular Dysfunction in Male Obese Insulin-Resistant Rats via Impairing Cardiac Mitochondrial Function and Dynamics Proteins

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis

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