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CTRP15 promotes macrophage cholesterol efflux and attenuates atherosclerosis by increasing the expression of ABCA1

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Abstract

C1q tumor necrosis factor–related protein 15 (CTRP15), a newly identified myokine, is closely implicated in cardiovascular disease. However, the role of CTRP15 in atherosclerosis is still unclear. This study aims to determine the role of CTRP15 in atherosclerosis and explore the underlying mechanisms. Our findings revealed that lentivirus-mediated CTRP15 overexpression significantly decreased atherosclerotic plaque lesions and increased reverse cholesterol transport (RCT) efficiency and circulating HDL-C levels in apolipoprotein E-deficient (apoE−/−) mice. Consistently, in vitro, overexpression of CTRP15 also inhibited intracellular lipid accumulation and promoted cholesterol efflux from macrophages. Mechanistically, CTRP15 decreased the expression of miR-101-3p by upregulating T-cadherin, thereby facilitating ABCA1 expression and cholesterol efflux. In summary, these data indicate that CTRP15 inhibits the development of atherosclerosis by enhancing RCT efficiency and increasing plasma HDL-C levels via the T-cadherin/miR-101-3p/ABCA1 pathway. Targeting CTRP15 may serve as a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases.

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Abbreviations

CTRP15:

C1q tumor necrosis factor-related protein 15

ApoE−/− :

Apolipoprotein E-deficient

CAD:

Coronary artery disease

PBS:

Phosphate-buffered saline

ApoA-I:

Apolipoprotein A-I

LV-NC:

Lentiviral empty vector

HDL:

High-density lipoprotein

TGFβ1:

Transforming growth factor-β1

TNF-α:

Tumor necrosis factor alpha

OCT:

Optimal cutting temperature

LDL-C:

LDL cholesterol

AdipoR1:

Adiponectin receptor 1

RCT:

Reverse cholesterol transport

PBS:

Phosphate-buffered saline

MPMs:

Mouse peritoneal macrophages

H&E:

Hematoxylin and eosin

ABCA1:

ATP-binding cassette transporter A1

TG:

Triglyceride

miRNAs:

MicroRNAs

TC:

Total cholesterol

IL-6:

Interleukin-6

HDL-C:

HDL-cholesterol

ac-LDL:

Acetylated-LDL

HPLC:

High-performance liquid chromatography

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Funding

This study was supported by the Hunan Natural Science Fund-Youth Foundation Project (No. 2021JJ40500) and the Scientific Research Project of the Hunan Health Commission (No. 20200410).

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Authors and Affiliations

  1. Department of Emergency Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China

    Wei-Hua Tan, Zheng-Liang Peng, Ting You & Zhi-Lu Sun

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  2. Zheng-Liang Peng
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  3. Ting You
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Contributions

Zhi-Lu Sun conceived and designed the experiments. Wei-Hua Tan, Zheng-Liang Peng, and Ting You performed the experiments. Wei-Hua Tan drafted and wrote the manuscript. Zheng-Liang Peng and Ting You analyzed the data. Zhi-Lu Sun provided materials and reagents. Final approval of manuscript: all authors. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Zhi-Lu Sun.

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This study was approved by the Animal Ethics Committee of the University of South China.

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Key points

1. CTRP15 inhibits atherosclerosis by promoting RCT and macrophage cholesterol efflux in apoE−/− mice.

2. CTRP15 upregulates ABCA1 expression and cholesterol efflux through downregulating the expression of miR-101-3p.

3. T-cadherin is required for the effect of CTRP15 on ABCA1 expression.

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Tan, WH., Peng, ZL., You, T. et al. CTRP15 promotes macrophage cholesterol efflux and attenuates atherosclerosis by increasing the expression of ABCA1. J Physiol Biochem 78, 653–666 (2022). https://doi.org/10.1007/s13105-022-00885-6

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  • DOI: https://doi.org/10.1007/s13105-022-00885-6

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