期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 316, 期 6, 页码 C888-C897出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00293.2018
关键词
human artery coronary smooth muscle cells; inflammation; lipid-laden cells; migration; oxidative stress; proliferation
资金
- Spanish Biomedical Research Centre in Diabetes and the Associated Metabolic Disorders (CIBERDEM)
- Instituto Carlos III [FIS-PI10/02547]
- Fondo Europeo de Desarrollo Regional funds
Fatty acids are essential to cell functionality and may exert diverging vascular effects including migration, proliferation, oxidative stress, and inflammation. This study examined the effect of palmitate on human coronary artery smooth muscle cell (HCASMC) function. An in vitro wound-healing assay indicated that palmitate decreased HCASMC migration in dose- and time-dependent manners. Furthermore, bromodeoxyuridine incorporation assays indicated that palmitate decreased HCASMC proliferation in a dose-response manner. Palmitate also increased reactive oxygen species formation, malondialdehyde content, and intracellular lipid droplets accompanied with increased fatty acid binding protein 4 expression. Moreover, palmitate induced gene expression (monocyte chemoattractant protein 1, matrix metalloproteinase-2, IL-1 beta, IL-6, IL-8, and TNF-alpha) and intracellular protein content (plasminogen activator inhibitor-1 and urokinase plasminogen activator) of inflammatory mediators. Finally, we showed that palmitate activates the transcription factor Nrf2 and the upstream kinases ERK1/2 and Akt in HCASMCs. The inhibitor of Nrf2, trigonelline, significantly attenuated palmitate-induced HCASMC expression of the Nrf2 target gene NQO1. These findings indicate that palmitate might be critically related to HCASMC function by slowing cell migration and proliferation and inducing lipid-laden cells, oxidative stress, and inflammation in part by activation of the Nrf2 transcription factor. Palmitate's activation of proinflammatory Nrf2 signaling may represent a novel mechanism mediating the proatherogenic actions of saturated fatty acids.
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