PMID- 37371838 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230701 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 11 IP - 6 DP - 2023 Jun 17 TI - Mannose-Binding Lectin Reduces Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cells Injury by Inhibiting LOX1-ox-LDL Binding and Modulating Autophagy. LID - 10.3390/biomedicines11061743 [doi] LID - 1743 AB - 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. FAU - Zhou, Xuelian AU - Zhou X AUID- ORCID: 0000-0002-0240-0652 AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Chen, Xuefeng AU - Chen X AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Zhang, Li AU - Zhang L AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Yuan, Jinna AU - Yuan J AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Lin, Hu AU - Lin H AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Zhu, Mingqiang AU - Zhu M AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Xu, Xiaoqin AU - Xu X AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Dong, Guanping AU - Dong G AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Fu, Junfen AU - Fu J AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. FAU - Wu, Wei AU - Wu W AD - Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China. LA - eng GR - 81471056/National Natural Science Foundation of China/ GR - 2022KY870/the Clinical research application project of Zhejiang Province Health science and Technology Plan/ GR - 2021YFC2701901/the National Key Research and Development Program of China/ GR - LSZ19H070001/Zhejiang Province Natural Sciences Foundation Zhejiang Society for Mathematical Medicine/ GR - LGF21H070004/Zhejiang Provincial Key Science and Technology Project/ GR - 2020XZZX002-22/the Fundamental Research Funds for the Central Universities/ PT - Journal Article DEP - 20230617 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC10296346 OTO - NOTNLM OT - LOX1 OT - atherosclerosis OT - autophagy OT - endothelial cells injury OT - mannose-binding lectin COIS- The authors declare no conflict of interest. EDAT- 2023/06/28 06:42 MHDA- 2023/06/28 06:43 PMCR- 2023/06/17 CRDT- 2023/06/28 01:09 PHST- 2023/04/23 00:00 [received] PHST- 2023/06/05 00:00 [revised] PHST- 2023/06/14 00:00 [accepted] PHST- 2023/06/28 06:43 [medline] PHST- 2023/06/28 06:42 [pubmed] PHST- 2023/06/28 01:09 [entrez] PHST- 2023/06/17 00:00 [pmc-release] AID - biomedicines11061743 [pii] AID - biomedicines-11-01743 [pii] AID - 10.3390/biomedicines11061743 [doi] PST - epublish SO - Biomedicines. 2023 Jun 17;11(6):1743. doi: 10.3390/biomedicines11061743.