Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle-Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells

Zhao-Lin Zeng; Zhi-Bo Zhao; Qing Yuan; Shi-Qi Yang; Zhen-Xing Wang; Zuo Wang; Shi-Yu Zeng; An-Qi Li; Qian Chen; Guo-Qiang Zhu; Xin-Hua Xiao; Guang-Hua Luo; Hai-Yan Luo; Jiao-Yang Li; Xu-Yu Zu; Hui Xie; Jiang-Hua Liu

doi:10.1002/advs.202408660

Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle-Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells

Adv Sci (Weinh). 2024 Dec 16:e2408660. doi: 10.1002/advs.202408660. Online ahead of print.

Authors

Zhao-Lin Zeng^{1

2

3

4

5}, Zhi-Bo Zhao^{1

3

4}, Qing Yuan^{1

3

4}, Shi-Qi Yang^{1

3

4}, Zhen-Xing Wang⁶, Zuo Wang⁵, Shi-Yu Zeng^{1

3

4}, An-Qi Li^{1

3

4}, Qian Chen^{1

3

4}, Guo-Qiang Zhu⁶, Xin-Hua Xiao^{1

3

4}, Guang-Hua Luo⁷, Hai-Yan Luo⁸, Jiao-Yang Li⁹, Xu-Yu Zu^{1

3

4}, Hui Xie⁶, Jiang-Hua Liu^{1

3

4}

Affiliations

¹ Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P. R. China.
² Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
³ Diabetes Clinical Medical Research Center of Hunan Provincial, Hengyang, Hunan, 421001, P. R. China.
⁴ Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P. R. China.
⁵ Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P. R. China.
⁶ Department of Orthopedics, Movement System Injury and Repair Research Center, National Clinical Research Center for Geriatric Disorders, Hunan Key Laboratory of Angmedicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China.
⁷ Department of Radiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P. R. China.
⁸ Department of Gastroenterology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P. R. China.
⁹ Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, 430071, P. R. China.

PMID: 39680681
DOI: 10.1002/advs.202408660

Abstract

The global incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) has risen sharply. This condition is strongly associated with the risk of cardiovascular disease (CVD), but how MAFLD affects the development and progression of CVD, particularly concerning vascular calcification, remains unclear. Herein, extracellular vesicles (EVs) are identified from steatotic hepatocytes as a trigger that accelerated the progression of both vascular intimal and medial calcification. Steatotic hepatocytes are found to release more EVs, which are able to reach the vascular tissue, be taken up by vascular smooth muscle cells (VSMCs), and promote their osteogenic differentiation. Within these toxic vesicles, a protein cargo is identified called lectin galactoside-binding soluble 3 binding protein (Lgals3bp) that acted as a potent inducer of osteochondrogenic transformation in VSMCs. Both the inhibition of EV release and the liver-specific knockdown of Lgals3bp profoundly attenuated vascular calcification. This work partially explains the reason for the high incidence of vascular calcification in MAFLD and unveils a novel mechanism that may be used to prevent or treat cardiovascular complications in patients with MAFLD.

Keywords: Lgals3bp; MAFLD; atherosclerosis; extracellular vesicles; vascular calcification.

Abstract

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