Macrophage galectin-3 enhances intimal translocation of vascular calcification in diabetes mellitus

被引：25

作者：

Sun, Zhen ^{[1
]}

Li, Lihua ^{[2
]}

Zhang, Lili ^{[1
]}

Yan, Jinchuan ^{[1
]}

Shao, Chen ^{[1
]}

Bao, Zhengyang ^{[1
]}

Liu, Jia ^{[1
]}

Li, Yalan ^{[1
]}

Zhou, Mengxue ^{[1
]}

Hou, Lina ^{[1
]}

Jing, Lele ^{[1
]}

Pang, Qiwen ^{[1
]}

Geng, Yue ^{[1
]}

Mao, Xiang ^{[1
]}

Gu, Wen ^{[1
]}

Wang, Zhongqun ^{[1
]}

机构：

[1] Jiangsu Univ, Dept Cardiol, Affiliated Hosp, Zhenjiang 212001, Jiangsu, Peoples R China

[2] Jiangsu Univ, Dept Pathol, Affiliated Hosp, Zhenjiang, Jiangsu, Peoples R China

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2020年 / 318卷 / 05期

基金：

中国国家自然科学基金;

关键词：

extracellular vesicle; galectin-3; macrophage; vascular calcification; vascular smooth muscle cell; SMOOTH-MUSCLE-CELLS; MEDIAL ARTERY CALCIFICATION; ATHEROSCLEROTIC PLAQUE; MATRIX VESICLES; MOUSE-MODEL; ASSOCIATION; DIFFERENTIATION; INFLAMMATION; PROGRESSION; MANAGEMENT;

D O I：

10.1152/ajpheart.00690.2019

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation. The patients were then divided into VIC and VMC groups. There were plaques in all anterior tibial arteries, while the enrichment of galectin-3 in arterial plaques in the VIC group was significantly higher than that in the VMC group. Furthermore, a macrophage/vascular smooth muscle cell (VSMC) coculture system was constructed. VSMC-derived extracellular vesicles (EVs) was labeled with fluorescent probe. After macrophages were pretreated with recombinant galectin-3 protein, the migration of VSMC-derived EVs and VSMC-derived calcification was more pronounced. And anti-galectin-3 antibody can inhibit this process of EVs and calcification translocation. Then, lentivirus (LV)-treated bone marrow cells (BMCs) were transplanted into apolipoprotein E-deficient (ApoE(-/-)) mice, and a diabetic atherosclerosis mouse model was constructed. After 15 wk of high-fat diet, ApoE(-/-) mice trans- planted with LV-shgalectin-3 BMCs exhibited medial calcification and a concentrated distribution of EVs in the media. In conclusion, upregulation of galectin-3 in macrophages promotes the migration of VSMC-derived EVs to the intima and induces diabetic vascular intimal calcification. NEW & NOTEWORTHY The clinical risk and prognosis of vascular intimal and medial calcification are different. Macrophage galectin-3 regulates the migration of vascular smooth muscle cellderived extracellular vesicles and mediates diabetic vascular intimal/medial calcification translocation. This study may provide insights into the early intervention in diabetic vascular calcification.

引用

页码：H1068 / H1079

页数：12

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