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Krüppel-like factor 14 inhibits atherosclerosis via mir-27a-mediated down-regulation of lipoprotein lipase expression in vivo
- Source :
- Atherosclerosis. 289:143-161
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Background and aims Kruppel-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 and results 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.
- Subjects :
- Male
0301 basic medicine
Apolipoprotein E
Mice, Knockout, ApoE
Kruppel-Like Transcription Factors
Down-Regulation
KLF14
Inflammation
030204 cardiovascular system & hematology
Transfection
Gene Expression Regulation, Enzymologic
Proinflammatory cytokine
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Homeostasis
Lipoprotein lipase
Plant Extracts
Chemistry
Macrophages
Lipid metabolism
Atherosclerosis
Lipid Metabolism
Lipids
Gynostemma
Cell biology
Lipoproteins, LDL
Lipoprotein Lipase
MicroRNAs
RAW 264.7 Cells
030104 developmental biology
lipids (amino acids, peptides, and proteins)
medicine.symptom
Cardiology and Cardiovascular Medicine
Chromatin immunoprecipitation
Lipoprotein
Subjects
Details
- ISSN :
- 00219150
- Volume :
- 289
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....0c25151b21ded5b36aacb1dba62268e5