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CTRP12 ameliorates post-myocardial infarction heart failure through down-regulation of cardiac apoptosis, oxidative stress and inflammation by influencing the TAK1-p38 MAPK/JNK pathway

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Abstract

Objective

C1q/tumour necrosis factor-related protein 12 (CTRP12) is closely related to coronary artery disease and has an outstanding cardioprotective effect. However, whether CTRP12 participates in heart failure (HF) has not been well studied. This work aimed to explore the role and mechanism of CTRP12 in post-myocardial infarction (MI) HF.

Methods

Rats were subjected to left anterior descending artery ligation and then raised for six weeks to establish post-MI HF. Recombinant adeno-associated virus-mediated gene transfer was applied to overexpress or silence CTRP12 in rat hearts. RT-qPCR, Immunoblot, Echocardiography, Haematoxylin–eosin (HE) staining, Masson’s trichrome staining, TUNEL staining and ELISA were carried out.

Results

CTRP12 levels were decreased in the hearts of rats with post-MI HF. The overexpression of CTRP12 improved cardiac function and attenuated cardiac hypertrophy and fibrosis in rats with post-MI HF. CTRP12 silencing exacerbated cardiac dysfunction, hypertrophy and fibrosis in rats with post-MI HF. The cardiac apoptosis, oxidative stress and inflammatory response induced by post-MI HF were weakened by CTRP12 overexpression or aggravated by CTRP12 silencing. CTRP12 inhibited the activation of the transforming growth factor‐β activated kinase 1 (TAK1)-p38 mitogen‐activated protein kinase (MAPK)/c‐Jun N‐terminal kinase (JNK) pathway in the hearts of rats with post-MI HF. Treatment with the TAK1 inhibitor reversed the adverse effects of CTRP12 silencing on post-MI HF.

Conclusions

CTRP12 protects against post-MI HF by modulating the TAK1-p38 MAPK/JNK pathway. CTRP12 may be a therapeutic target for the treatment of post-MI HF.

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Data availability

The datasets used during the present study are available from the corresponding author on reasonable request.

Abbreviations

CTRP12:

C1q/tumour necrosis factor-related protein 12

HF:

Heart failure

MI:

Myocardial infarction

TAK1:

Transforming growth factor‐β activated kinase 1

MAPK:

Mitogen‐activated protein kinase

JNK:

C‐Jun N‐terminal kinase

AAV:

Adeno-associated virus

LVEF:

Left ventricular ejection fraction

LVFS:

Left ventricular fractional shortening

ELISA:

Enzyme-linked immunosorbent assay

NT-proBNP:

N-terminal pro-brain natriuretic peptide

IL:

Interleukin

HE:

Haematoxylin–eosin

TNF:

Tumour necrosis factor

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Funding

The work was supported by the Science and Technology Innovation and Development Fund of Tangdu Hospital (2019QYTS011).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710048, China

    Baobao Bai & Yue Wu

  2. Department of Cardiology, Tangdu Hospital, Air Force Medical University, Xi’an, 710038, China

    Baobao Bai, Zhaole Ji, Fangfang Wang, Chaoshi Qin, Haijia Zhou & Dongdong Li

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  1. Baobao Bai
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  2. Zhaole Ji
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  3. Fangfang Wang
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  4. Chaoshi Qin
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  7. Yue Wu
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Contributions

BB designed the work, performed the experiments and wrote the manuscript. ZJ, FW and CQ performed the experiments. HZ and DL performed data analysis and provided technical support. Yue Wu contributed to conceptualization and reviewed the manuscript.

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Correspondence to Yue Wu.

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Bai, B., Ji, Z., Wang, F. et al. CTRP12 ameliorates post-myocardial infarction heart failure through down-regulation of cardiac apoptosis, oxidative stress and inflammation by influencing the TAK1-p38 MAPK/JNK pathway. Inflamm. Res. 72, 1375–1390 (2023). https://doi.org/10.1007/s00011-023-01758-4

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  • DOI: https://doi.org/10.1007/s00011-023-01758-4

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