The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis

被引:36
作者
Chen, Jiefang [1 ]
Su, Ying [1 ]
Pi, Shulan [1 ]
Hu, Bo [1 ]
Mao, Ling [1 ]
机构
[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurol, Wuhan, Peoples R China
来源
FRONTIERS IN CARDIOVASCULAR MEDICINE | 2021年 / 8卷
基金
中国国家自然科学基金;
关键词
LRP1; atherosclerosis; smooth muscle cells; macrophages; endothelial cells; adipocytes; immune cells; SMOOTH-MUSCLE-CELLS; HEPARAN-SULFATE PROTEOGLYCANS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; LDL-RECEPTOR; GROWTH-FACTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; AGGREGATED LDL; CELLULAR INTERNALIZATION; ALPHA(2)-MACROGLOBULIN RECEPTOR; ENDOCYTIC RECEPTOR;
D O I
10.3389/fcvm.2021.682389
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Low-density lipoprotein receptor-related protein-1 (LRP1) is a large endocytic and signaling receptor belonging to the LDL receptor (LDLR) gene family and that is widely expressed in several tissues. LRP1 comprises a large extracellular domain (ECD; 515 kDa, alpha chain) and a small intracellular domain (ICD; 85 kDa, beta chain). The deletion of LRP1 leads to embryonic lethality in mice, revealing a crucial but yet undefined role in embryogenesis and development. LRP1 has been postulated to participate in numerous diverse physiological and pathological processes ranging from plasma lipoprotein homeostasis, atherosclerosis, tumor evolution, and fibrinolysis to neuronal regeneration and survival. Many studies using cultured cells and in vivo animal models have revealed the important roles of LRP1 in vascular remodeling, foam cell biology, inflammation and atherosclerosis. However, its role in atherosclerosis remains controversial. LRP1 not only participates in the removal of atherogenic lipoproteins and proatherogenic ligands in the liver but also mediates the uptake of aggregated LDL to promote the formation of macrophage- and vascular smooth muscle cell (VSMC)-derived foam cells, which causes a prothrombotic transformation of the vascular wall. The dual and opposing roles of LRP1 may also represent an interesting target for atherosclerosis therapeutics. This review highlights the influence of LRP1 during atherosclerosis development, focusing on its dual role in vascular cells and immune cells.
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页数:20
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