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Int J Biol Sci 2024; 20(6):2092-2110. doi:10.7150/ijbs.93544 This issue Cite

Research Paper

Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis

Min Chen1*, Dafeng Yang2*, Yangzhao Zhou2, Chongzhe Yang3, Wenhui Lin1, Jie Li1, Jitao Liu1, Jiamin Ye1, Wenhui Huang1, Wentao Ma1, Wei Li4, Jiyan Chen1, Ying Zhang1, Guo-Ping Shi5, Jianfang Luo1✉, Jie Li3✉, Songyuan Luo6,7✉

1. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China.
2. Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
3. Department of Geriatrics, National Key Clinic Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
4. Department of Cardiology, Guangdong Provincial People's Hospital Zhuhai Hospital, Zhuhai, China.
5. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
6. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Hypertension, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China.
7. Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.
* These authors contributed equally to this work.

✉ Corresponding authors: Jianfang Luo, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Southern Medical University, Dongchu More

Citation:
Chen M, Yang D, Zhou Y, Yang C, Lin W, Li J, Liu J, Ye J, Huang W, Ma W, Li W, Chen J, Zhang Y, Shi GP, Luo J, Li J, Luo S. Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis. Int J Biol Sci 2024; 20(6):2092-2110. doi:10.7150/ijbs.93544. https://www.ijbs.com/v20p2092.htm
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Abstract

Graphic abstract

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models. Mechanistically, colchicine increased global mRNA stability by inhibiting the METTL14/YTHDC1-mediated m6A modification, resulting in increased sclerostin (SOST) expression and consequent inactivation of the WNT/β-catenin signaling pathway in vascular SMCs from mouse AAA lesions and in cultured human aortic SMCs. Moreover, human and mouse AAA lesions all showed increased m6A methylation, decreased SOST expression, and skewed synthetic SMC de-differentiation phenotype, compared to those without AAA. This study uncovers a novel mechanism of colchicine in slowing AAA development by using the METTL14/SOST/WNT/β-catenin axis to control vascular SMC homeostasis in mouse aortic vessels and in human aortic SMCs. Therefore, use of colchicine may benefit AAA patients in clinical practice.

Keywords: abdominal aortic aneurysm, colchicine, vascular smooth muscle cell, sclerostin, N6-methyladenosine

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APA
Chen, M., Yang, D., Zhou, Y., Yang, C., Lin, W., Li, J., Liu, J., Ye, J., Huang, W., Ma, W., Li, W., Chen, J., Zhang, Y., Shi, G.P., Luo, J., Li, J., Luo, S. (2024). Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis. International Journal of Biological Sciences, 20(6), 2092-2110. https://doi.org/10.7150/ijbs.93544.

ACS
Chen, M.; Yang, D.; Zhou, Y.; Yang, C.; Lin, W.; Li, J.; Liu, J.; Ye, J.; Huang, W.; Ma, W.; Li, W.; Chen, J.; Zhang, Y.; Shi, G.P.; Luo, J.; Li, J.; Luo, S. Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis. Int. J. Biol. Sci. 2024, 20 (6), 2092-2110. DOI: 10.7150/ijbs.93544.

NLM
Chen M, Yang D, Zhou Y, Yang C, Lin W, Li J, Liu J, Ye J, Huang W, Ma W, Li W, Chen J, Zhang Y, Shi GP, Luo J, Li J, Luo S. Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis. Int J Biol Sci 2024; 20(6):2092-2110. doi:10.7150/ijbs.93544. https://www.ijbs.com/v20p2092.htm

CSE
Chen M, Yang D, Zhou Y, Yang C, Lin W, Li J, Liu J, Ye J, Huang W, Ma W, Li W, Chen J, Zhang Y, Shi GP, Luo J, Li J, Luo S. 2024. Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis. Int J Biol Sci. 20(6):2092-2110.

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