AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025250266
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ORIGINAL RESEARCH ARTICLE

Whole-body Metrnl knockout, but not bone marrow-specific knockout, aggravates atherosclerosis

Si-Li Zheng1† ,  Zhu-Wei Miao1† ,  Pin Wang1 ,  Xue-Lian Wang1 ,  Chao-Yu Miao1*
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1 Department of Pharmacology, School of Pharmacy, Second Military Medical University/Naval Medical University, Shanghai, China
†These authors contributed equally to this work.
EJMO, 025250266 https://doi.org/10.36922/EJMO025250266
Received: 20 June 2025 | Revised: 27 August 2025 | Accepted: 19 November 2025 | Published online: 13 March 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Meteorin-like protein (Metrnl) is a secreted protein. Circulating Metrnl primarily originates from the vascular endothelium and has been identified as a regulator of endothelial function and atherosclerosis.

Objective: This study aims to investigate the effects of whole-body Metrnl knockout and bone marrow (BM)-specific Metrnl knockout on atherosclerosis.

Methods: A mouse atherosclerosis model with whole-body Metrnl knockout (Apoe−/−Metrnl−/−) was established. Using BM transplantation, a second model with BM-specific Metrnl knockout (chimeric Apoe−/− mice with BM from Apoe−/−Metrnl−/− mice) was generated. Successful knockouts mice were verified by real-time polymerase chain reaction and Western blot analysis. After several weeks on a highfat diet, atherosclerotic lesions and related inflammation indices in the aortas of both Apoe−/−Metrnl−/− and BM-Metrnl−/− mice were assessed using Oil Red O staining and immunohistochemistry.

Results: After 10 or 16 weeks on a high-fat diet, Apoe−/−Metrnl−/− mice developed more extensive atherosclerotic plaques in the aorta compared to their littermate controls, exhibiting increased plaque burden and inflammation at the aortic roots. In contrast, BM-Metrnl−/− mice showed successful Metrnl knockout in BM, yet after 16 weeks on a high-fat diet, they developed atherosclerotic plaques comparable to those of controls.

Conclusion: These results suggest that whole-body Metrnl knockout aggravates atherosclerosis development, whereas the role of BM-derived Metrnl in atherosclerosis occurrence is not apparent.

Graphical abstract
Keywords
Meteorin-like protein
Atherosclerosis
Whole-body knockout
Bone marrow
Aorta
Inflammation
Funding
This work was supported by the National Natural Science Foundation of China Major Project (grant no.: 82030110), the National Natural Science Foundation of China Young Program (grant no.: 82104165), and the Shanghai Sailing Program (grant no.: 21YF1457600).
Conflict of interest
The authors declare no conflict of interest, financial or otherwise.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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