Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells
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 calcifi...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202408660 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540916206796800 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Zhao‐Lin Zeng |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c1a50c6b15bf498a877ad21df68ab73d |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-c1a50c6b15bf498a877ad21df68ab73d2025-02-04T13:14:55ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202408660Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle CellsZhao‐Lin Zeng0Zhi‐Bo Zhao1Qing Yuan2Shi‐Qi Yang3Zhen‐Xing Wang4Zuo Wang5Shi‐Yu Zeng6An‐Qi Li7Qian Chen8Guo‐Qiang Zhu9Xin‐Hua Xiao10Guang‐Hua Luo11Hai‐Yan Luo12Jiao‐Yang Li13Xu‐Yu Zu14Hui Xie15Jiang‐Hua Liu16Department of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment 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. ChinaInstitute of Cardiovascular Disease Key Lab for Arteriosclerology of Hunan Province Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment 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. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Radiology The First Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Gastroenterology The First Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Occupational and Environmental Health School of Public Health Wuhan University Wuhan 430071 P. R. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment 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. ChinaDepartment of Metabolism and Endocrinology The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaAbstract 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.https://doi.org/10.1002/advs.202408660atherosclerosisextracellular vesiclesLgals3bpMAFLDvascular calcification |
| spellingShingle | 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 Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells Advanced Science atherosclerosis extracellular vesicles Lgals3bp MAFLD vascular calcification |
| title | Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells |
| title_full | Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells |
| title_fullStr | Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells |
| title_full_unstemmed | Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells |
| title_short | Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle‐Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells |
| title_sort | hepatic steatosis aggravates vascular calcification via extracellular vesicle mediated osteochondrogenic switch of vascular smooth muscle cells |
| topic | atherosclerosis extracellular vesicles Lgals3bp MAFLD vascular calcification |
| url | https://doi.org/10.1002/advs.202408660 |
| work_keys_str_mv | AT zhaolinzeng hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT zhibozhao hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT qingyuan hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT shiqiyang hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT zhenxingwang hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT zuowang hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT shiyuzeng hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT anqili hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT qianchen hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT guoqiangzhu hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT xinhuaxiao hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT guanghualuo hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT haiyanluo hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT jiaoyangli hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT xuyuzu hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT huixie hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells AT jianghualiu hepaticsteatosisaggravatesvascularcalcificationviaextracellularvesiclemediatedosteochondrogenicswitchofvascularsmoothmusclecells |