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Autophagy-Sirtuin1(SIRT1) Alleviated the Coronary Atherosclerosis (AS) in Mice through Regulating the Proliferation and Migration of Endothelial Progenitor Cells (EPCs) via wnt/β-catenin/GSK3β Signaling Pathway

  • Original Research
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The journal of nutrition, health & aging

Abstract

Background and Purpose

SIRT1 was associated with AS risk and EPCs were reported to participate in the endothelial repair in Coronary Atherosclerosis (CAS). In this study, we explored the role of SIRT1 in AS mice and also its modulation in EPCs.

Methods and Materials

ApoE−/−mice were fed on high-fat and high-glucose diet to establish the AS animal model with the normally-raised C57BL/6 mice as a control group. SIRT1 activator, SRT 2104 was injected intravenously into 5 ApoE−/−mice and its inhibitor Nicotinamide was injected in tail in another 5 ApoE−/− mice. Weight changes were recorded. Blood samples were taken from posterior orbital venous plexus and were detected by automatic biochemical analyzer. HE staining displayed the pathological conditions while Immunohistochemistry (IHC) evaluated the CD34+/VEGFR2+ relative density in the aorta tissues. EPCs were isolated from bone marrow and verified using immunofluorescence staining (IFS). The modulatory mechanism of SIRT1 in EPCs were studied by using RT-PCR, MTT, Western Blot and colony formation, scratch methods.

Results

SIRT1 activator negatively regulated the weight and TC, TG and LDL levels, alleviated the lesion conditions and decreased the CD34+/VEGFR2+ density compared to the AS control. In vitro, SIRT1 activator promoted the proliferation and migration of EPCs and activated wnt/β-catenin/GSK3β signaling pathway. SIRT1 activator also inhibited the autophagy biomarkers ATG1 and LC3II. Furthermore, inhibitor of autophagy promoted SIRT1 expression and induced EPC proliferation, migration and activated wnt/β-catenin/GSK3β pathway. The suppression of the wnt/β-catenin/GSK3β pathway inhibited SIRT1 expression in EPCs, attenuated the proliferation and migration and promoted autophagy of EPCs.

Conclusion

SIRT1 activation might be protective in AS mice through autophagy inhibition in EPCs via wnt/β-catenin/GSK3β signaling pathway.

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Availability of data and material

All data are provided in this study and raw data can be requested to corresponding author.

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Funding

Funding: This work was supported by National Natural Science Foundation of China (Grant No. 81970303) Jinzhou science and technology guiding plan project (JZ2020B011) Horizontal scientific research project of Jinzhou Medical.

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Authors and Affiliations

  1. First Central Clinical College of Tianjin Medical University, Tianjin, China

    Y. Li

  2. Jinzhou Inspection and Testing Certification Center of Liaoning Province, Jinzhou, 121010, China

    W. Cui

  3. The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China

    B. Song

  4. Department of Cardiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, Tianjin, 300110, China

    X. Ye & C. Lu

  5. School of Medicine, Nankai University, Tianjin, China

    Z. Li

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Contributions

Yanwei Li- Literature search, DesignData, analysis, Statistical analysis, Manuscript review. Wei Cui- Concepts, Design, Data acquisition, Manuscript editing. Bing Song- Definition of intellectual content, Literature search. Xuying Ye-Experimental studies. Zhuqing Li- Manuscript preparation. Chengzhi Lu- Manuscript preparation, Manuscript review, Guarantor.

Corresponding author

Correspondence to C. Lu.

Ethics declarations

Ethical approval was obtained from Institutional ethical review Board (IEC) of The First Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning Province, China. Informed consent was obtained from the participants with the option to withdraw them from the study at any time. This work was supported by National Natural Science Foundation of China (Grant No. 81970303); Jinzhou science and technology guiding plan project (JZ2020B011); Horizontal scientific research project of Jinzhou Medical University; Project No. 2021007.

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Conflict of Interest

No conflict of interest was found or declared by any of authors.

Consent for publication

IEC of The First Affiliated Hospital, Jinzhou City, Liaoning Province, China affiliated to of Jinzhou Medical University, approved the publication of data generated from this study.

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Li, Y., Cui, W., Song, B. et al. Autophagy-Sirtuin1(SIRT1) Alleviated the Coronary Atherosclerosis (AS) in Mice through Regulating the Proliferation and Migration of Endothelial Progenitor Cells (EPCs) via wnt/β-catenin/GSK3β Signaling Pathway. J Nutr Health Aging 26, 297–306 (2022). https://doi.org/10.1007/s12603-022-1750-7

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  • DOI: https://doi.org/10.1007/s12603-022-1750-7

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