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Eicosapentaenoic Acid Preserves Mitochondrial Quality and Attenuates Cardiac Remodeling After Myocardial Infarction in Rats

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Abstract

Eicosapentaenoic acid (EPA) reduces the risk of ischemic heart diseases and is a component of mitochondria. We herein investigated whether dietary EPA mediated mitochondrial fatty acid compositions, dynamics, and functions, resulting in the attenuation of cardiac remodeling after myocardial infarction (MI). The coronary artery of male rats was ligated to induce MI, and they were then treated with or without EPA (1000 mg/kg/day) for 12 weeks. The EPA treatment improved left ventricular systolic function and increased the mitochondrial content of EPA in the non-infarct region 12 weeks after MI. The content of ATP and mitochondrial complex II, III, and IV activities decreased after MI but were maintained by the EPA treatment in association with the preservation of optic atrophy 1, a mitochondrial fusion protein. The present results suggest that dietary EPA increased the mitochondrial content of EPA and preserved the expression of mitochondrial fusion proteins and energy metabolism, which attenuated left ventricular remodeling after MI.

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Data Availability

The data used to support the present results are available upon request from the corresponding author.

Abbreviations

AA:

Arachidonic acid

ALA:

α-Linolenic acid

ATP:

Adenosine triphosphate

BSA:

Bovine serum albumin

BW:

Body weight

CHF:

Chronic heart failure

DGLA:

Dihomo-γ-linolenic acid

DHA:

Docosapentaenoic acid

Drp-1:

Dynamin-related protein 1

EGTA:

Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N′,N′-tetraacetic acid

EPA:

Eicosapentaenoic acid

GC-MS:

Gas chromatography–mass spectrometry

GLA:

γ-Linolenic acid

HE:

Hematoxylin-eosin

HW:

Heart weight

LV:

Left ventricular

LVEDd:

Left ventricular end-diastolic diameter

LVEDs:

Left ventricular end-systolic diameter

LVFS:

Left ventricular fractional shortening

LVW:

Left ventricular weight

LW:

Lung weight

MI:

Myocardial infarction

MOPS:

Morpholinepropanesulfonic acid

OPA1:

Optic atrophy 1

PUFA:

Polyunsaturated fatty acids

RBC:

Red blood cell

TA:

Tridecanoic acid

TG:

Triglyceride

TTC:

Triphenyl tetrazolium chloride

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Acknowledgements

We would like to thank Mochida Pharmaceutical Co., Ltd. (Tokyo, Japan) for supplying EPA.

Funding

This work was supported, in part, by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 24591102.

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Author notes

  1. Miyuki Kobara and Tatsuya Shiraishi contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, 5 Misasagi Nakauchi-cho, Yamashina-ku, Kyoto, 607-8414, Japan

    Miyuki Kobara, Tatsuya Shiraishi, Kazuki Noda, Hiroe Toba & Tetsuo Nakata

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  1. Miyuki Kobara
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  2. Tatsuya Shiraishi
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  3. Kazuki Noda
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  4. Hiroe Toba
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Contributions

All the authors contributed to the study conception and design. Miyuki Kobara designed and performed the experiments and wrote the first draft of the manuscript. Tatsuya Shiraishi performed the experiments and data analysis. Kazuki Noda performed the GC–MS measurement and analysis. Hiroe Toba performed the data analysis. Tetsuo Nakata contributed to the conception of the study and drafting of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Miyuki Kobara.

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Ethics Approval

All procedures conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. The protocol was approved by the Bioethics Committee of Kyoto Pharmaceutical University.

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No human studies were performed by the authors for this article.

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

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The authors declare no competing interests.

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Associate Editor Guo** Li oversaw the review of this article

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Kobara, M., Shiraishi, T., Noda, K. et al. Eicosapentaenoic Acid Preserves Mitochondrial Quality and Attenuates Cardiac Remodeling After Myocardial Infarction in Rats. J. of Cardiovasc. Trans. Res. 16, 816–827 (2023). https://doi.org/10.1007/s12265-023-10363-z

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