Mannose-Binding Lectin Reduces Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cells Injury by Inhibiting LOX1-ox-LDL Binding and Modulating Autophagy
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Published:2023-06-17
Issue:6
Volume:11
Page:1743
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ISSN:2227-9059
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Container-title:Biomedicines
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language:en
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Short-container-title:Biomedicines
Author:
Zhou Xuelian1ORCID,
Chen Xuefeng1,
Zhang Li1,
Yuan Jinna1,
Lin Hu1,
Zhu Mingqiang1,
Xu Xiaoqin1,
Dong Guanping1,
Fu Junfen1,
Wu Wei1
Affiliation:
1. Department of Endocrinology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China
Abstract
Objective: To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL)-induced injury. Methods: Serum MBL concentration and carotid intima-media thickness (cIMT) were measured in 94 obese and 105 healthy children. ECs were transfected with MBL over-expression plasmid, LOX1 was knocked-down to explore the protective role of MBL in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, and inflammatory factors, DC maturation, and autophagy was assessed. WT and ApoE−/− mice were fed with a high fat diet (HFD) with or without MBL-adenovirus injection for 16 weeks and aortic vascular endothelial tissue was isolated, then atherosclerotic plaque, cell injury and autophagy were analyzed. Results: Serum MBL concentration in obese children was lower than healthy controls and was negatively correlated with cIMT. The uptake of ox-LDL was decreased in LOX1 knock-down ECs. MBL over-expression in vitro inhibited LOX1-ox-LDL binding. Both LOX1 knock-down and MBL over-expression can ameliorate EC autophagy and cell injury. MBL over-expression in vivo alleviated atherosclerotic plaque formation, influenced DC maturation and down-regulated IL-6, IL-12, and TNF-a levels. Conclusions: MBL exerts a protective role in ox-LDL-induced EC injury by modulating DC maturation and EC autophagy via inhibiting LOX1-ox-LDL binding.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Clinical research application project of Zhejiang Province Health Science and Technology Plan
Zhejiang Province Natural Sciences Foundation and Zhejiang Society for Mathematical Medicine
Zhejiang Provincial Key Science and Technology Project
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)