CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2018-01, Vol.97, p.1020-1031
Main Authors: Xu, Suining, Li, Lihua, Yan, Jinchuan, Ye, Fei, Shao, Chen, Sun, Zhen, Bao, Zhengyang, Dai, Zhiyin, Zhu, Jie, Jing, Lele, Wang, Zhongqun
Format: Article
Language:English
Subjects:
Animals
Aorta - metabolism
Apolipoproteins E - genetics
Atherosclerosis
Atherosclerosis - pathology
CD36
CD36 Antigens - metabolism
Cell migration
Cell Migration Inhibition - physiology
Cell Movement
Cholesterol - metabolism
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Type 2 - complications
Disease Models, Animal
Disease Progression
Foam cells
Foam Cells - metabolism
Glycation End Products, Advanced - metabolism
Lysine - analogs & derivatives
Lysine - metabolism
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Nε-carboxymethyl-lysine
Plaque, Atherosclerotic - pathology
RAW 264.7 Cells
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Summary:Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE−/− mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2017.11.041