LncRNA MIAT sponges miR-149-5p to inhibit efferocytosis in advanced atherosclerosis through CD47 upregulation

Atherosclerotic cardio-cerebrovascular disease and death remain the leading cause of morbidity and mortality worldwide. Defective efferocytosis, the clearance of apoptotic cells by macrophages, is thought to lead to increased inflammation and necrotic core formation in atherosclerotic lesions. Howev...

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Bibliographic Details
Published in:Cell death & disease 2019-02, Vol.10 (2), p.138-138, Article 138
Main Authors: Ye, Zi-ming, Yang, Shuai, Xia, Yuan-peng, Hu, Rui-ting, Chen, Shengcai, Li, Bo-wei, Chen, Shao-li, Luo, Xue-ying, Mao, Ling, Li, Yanan, Jin, Huijuan, Qin, Chao, Hu, Bo
Format: Article
Language:English
Subjects:
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14/19
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59/57
631/337/384/2568
64/60
692/699/75/593/2100
82/51
96/31
Aged
Animals
Antibodies
Apoptosis
Arteriosclerosis
Atherosclerosis
Biochemistry
Biomedical and Life Sciences
Carotid Artery Diseases - blood
CD47 Antigen - metabolism
Cell Biology
Cell Culture
Cerebrovascular diseases
Disease Models, Animal
Female
Gene Knockdown Techniques
HEK293 Cells
Humans
Immunology
Life Sciences
Macrophages
Macrophages - metabolism
Male
Mice
Mice, Knockout, ApoE
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miRNA
Morbidity
Myocardial infarction
Phagocytes
Phagocytosis - genetics
Plaques
RAW 264.7 Cells
RNA, Long Noncoding - blood
RNA, Long Noncoding - genetics
Transcription
Transfection
Up-Regulation
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Summary:Atherosclerotic cardio-cerebrovascular disease and death remain the leading cause of morbidity and mortality worldwide. Defective efferocytosis, the clearance of apoptotic cells by macrophages, is thought to lead to increased inflammation and necrotic core formation in atherosclerotic lesions. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here we show that lncRNA myocardial infarction associated transcript (MIAT) was markedly elevated in the serum of patients with symptoms of vulnerable atherosclerotic plaque and the macrophages of necrotic cores in an advanced atherosclerosis mouse model. MIAT knockdown attenuated atherosclerosis progression, reduced necrotic core size, and increased plaque stability in vivo. Furthermore, MIAT knockdown promoted clearance of apoptotic cells by macrophages in vivo and in vitro. Mechanistic studies revealed that MIAT acted as a micro RNA (miRNA) sponge to positively modulate the expression of anti-phagocytic molecule CD47 through sponging miR-149-5p. Together, these findings identified a macrophage MIAT/miR-149-5p /CD47 pathway as a key factor in the development of necrotic atherosclerotic plaques.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-019-1409-4