Journal
ATHEROSCLEROSIS
Volume 289, Issue -, Pages 143-161Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2019.08.012
Keywords
Kruppel-like factor; MicroRNA; Lipoprotein lipase; Inflammation; Macrophage; Atherosclerosis
Funding
- National Natural Science Foundation of China of China [81800386]
- Hunan Provincial Natural Science Foundation of China [2017JJ2234, 2018JJ3453]
- start-up funds for Ph.Ds in University of South China [2017XQD12, 2017XQD05]
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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 atherosclerosiscausing 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.
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