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FABP5 Deficiency Impairs Mitochondrial Function and Aggravates Pathological Cardiac Remodeling and Dysfunction

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Abstract

Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family and plays a vital role in the metabolism of fatty acids. However, few studies have examined the role of FABP5 in pathological cardiac remodeling and heart failure. The aim of this study was to explore the role of FABP5 in transverse aortic constriction (TAC)-induced pathological cardiac remodeling and dysfunction in mice. Quantitative RT-PCR (qRT-PCR) and western blotting (WB) analysis showed that the levels of FABP5 mRNA and protein, respectively, were upregulated in hearts of the TAC model. Ten weeks after TAC in FABP5 knockout and wild type control mice, echocardiography, histopathology, qRT-PCR, and WB demonstrated that FABP5 deficiency aggravated cardiac injury (both cardiac hypertrophy and fibrosis) and dysfunction. In addition, transmission electron microscopy, ATP detection, and WB revealed that TAC caused severe impairment to mitochondria in the hearts of FABP5-deficient mice compared with that in control mice. When FABP5 was downregulated by siRNA in primary mouse cardiac fibroblasts, FABP5 silencing increased oxidative stress, reduced mitochondrial respiration, and increased the expression of myofibroblast activation marker genes in response to treatment with transforming growth factor-β. Our findings demonstrate that FABP5 deficiency aggravates cardiac pathological remodeling and dysfunction by damaging cardiac mitochondrial function.

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The data supporting the findings of this study are included in the manuscript. The source data are provided in Tables 1–2, Figs. 1–6, and Online Resource 1.

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Acknowledgements

We are grateful to Professor Moshi Song (Chinese Academy of Sciences, Beijing, China) for their helpful advice.

Funding

This study was supported by grants from the National Science Foundation of China (Grant Number, 81790622), and Beijing Collaborative Innovative Research Center for Cardiovascular Diseases.

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Authors and Affiliations

  1. Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China

    Shanquan Gao, Guoqi Li, Yihui Shao, Zhipeng Wei, Shan Huang, Feiran Qi, Yao Jiao, Yulin Li, Congcong Zhang & Jie Du

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  1. Shanquan Gao
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  2. Guoqi Li
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  3. Yihui Shao
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Contributions

S.G., C.Z., Y.L., and J.D. conceived the project, designed the experiments, and wrote the paper. S.G., G.L., Y.S., Z.W., and S.H. performed the in vivo work. S.G., F.Q., and Y.J. performed the in vitro work. All authors read and approved the final manuscript.

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Correspondence to Congcong Zhang or Jie Du.

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All authors involved in this manuscript consent to its publication in Cardiovascular Toxicology in accordance with the journal's rules and regulations.

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All animal experiments were approved by the Animal Care and Utilization Committee of Capital Medical University and performed in accordance with the guidelines of the Capital Medical University.

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Gao, S., Li, G., Shao, Y. et al. FABP5 Deficiency Impairs Mitochondrial Function and Aggravates Pathological Cardiac Remodeling and Dysfunction. Cardiovasc Toxicol 21, 619–629 (2021). https://doi.org/10.1007/s12012-021-09653-2

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