Krüppel-like factor 14 inhibits atherosclerosis via mir-27a-mediated down-regulation of lipoprotein lipase expression in vivo.
Atherosclerosis
; 289: 143-161, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31518965
ABSTRACT
BACKGROUND AND AIMS:
Krüppel-like factor 14 (KLF14) is known to play a role in atherosclerosis, but the underlying mechanisms are still largely unknown. The aim of our study was to explore the effects of KLF14 on lipid metabolism and inflammatory response, providing a potential target for lowering the risk of atherosclerosis-causing disease. METHODS ANDRESULTS:
mRNA and protein levels of KLF14 were significantly decreased in oxidized low-density lipoprotein (oxLDL)-treated macrophages and in the atherosclerotic lesion area. Chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays were used to confirm that KLF14 positively regulated miR-27a expression by binding to its promoter. We also found that KLF14 could restored appropriate cellular lipid homeostasis and inflammatory responses via negatively regulating lipoprotein lipase (LPL) expression in THP1-derived macrophages through miR-27a. In addition, gypenosides (GP), a KLF14 activator, delayed the development of atherosclerosis in apolipoprotein E deficient (apoE-/-) mice.CONCLUSIONS:
KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Aterosclerose
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Fatores de Transcrição Kruppel-Like
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Lipase Lipoproteica
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article