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Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy

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Abstract

Background

Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL).

Methods and results

Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats.

Conclusion

VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart.

Graphical abstract

The illustration of the suggested mechanism underlying of Vitamin D in cardiac hypertrophy induced by aging

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Data Availability

The data used and analyzed in this study are available from the Corresponding author upon reasonable request.

Abbreviations

ANOVA:

Analysis of variance

Bax :

Bcl-2-associated X protein

Bcl-2 :

B-cell lymphoma 2

BW:

Body Weight

CH:

Cardiac hypertrophy

D-GAL:

D-galactose

Drp1 :

Dynamin-related protein 1

HW:

Heart Weight

i.p.:

Intraperitoneally

PINK1 :

tensin homologue (PTEN)-induced putative kinase 1

QRT-PCR:

Quantitative Real-Time PCR

ROS:

Reactive oxygen species

SE:

Standard error

VitD:

Vitamin D

VDR:

VitD receptor

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Acknowledgements

The authors would like to thank and appreciate the Hamadan University of Medical Sciences for funding the present research.

Funding

This study was funded by the Vice-Chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 140005124073).

Author information

Author notes

  1. Siamak Shahidi and Khadijeh Ramezani-Aliakbari contributed equally to this work and shared first authorship.

Authors and Affiliations

  1. Department of Physiology, School of medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Siamak Shahidi, Parisa Habibi & Fatemeh Ramezani-Aliakbari

  2. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Siamak Shahidi, Alireza Komaki, Iraj Salehi, Parisa Habibi & Fatemeh Ramezani-Aliakbari

  3. Department of Neuroscience, School of Sciences and Advanced Technology in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Siamak Shahidi, Alireza Komaki & Iraj Salehi

  4. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Khadijeh Ramezani-Aliakbari

  5. Medical School, Hamadan University of Medical Sciences, Hamadan, Iran

    Sayedpayam Hashemi

  6. Anatomy Department, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Sara Soleimani Asl

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  1. Siamak Shahidi
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Contributions

SSh and KHR-A contributed to data collection and interpretation and wrote the manuscript. AK performed the experiments and provided reagents.IS conceived and designed the experiments.SH provided reagents and materials and analyzed the data. SSA and PH contributed to data collection and analysis.FR-A designed the study, contributed to data collection and interpretation, and wrote the manuscript.

Corresponding author

Correspondence to Fatemeh Ramezani-Aliakbari.

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The authors declare no competing interests.

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Ethical approval was granted by the Ethics Committee of Hamadan University of Medical Sciences (Ethics code: IR.UMSHA.REC.1400.269).

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Shahidi, S., Ramezani-Aliakbari, K., Komaki, A. et al. Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy. Mol Biol Rep 50, 10147–10155 (2023). https://doi.org/10.1007/s11033-023-08875-7

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  • DOI: https://doi.org/10.1007/s11033-023-08875-7

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