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Am J Physiol Cell Physiol. 2019 Mar 13. doi: 10.1152/ajpcell.00293.2018. [Epub ahead of print]

Palmitate decreases migration and proliferation and increases oxidative stress and inflammation in smooth muscle cells. Role of the Nrf2 signaling pathway.

Author information

1
Research Unit on Lipid and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.

Abstract

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, BrdU incorporation assays indicated that palmitate decreased HCASMC proliferation in a dose-response manner. Palmitate also increased ROS formation, MDA content and intracellular lipid droplets accompained with an increased of FABP4 expression. Moreover, palmitate induced gene expression (MCP1, MMP2, IL-1β, IL-6, IL-8 and TNF-α) and intracellular protein content (PAI-1 and uPA) 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, trigonellin, 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 pro-inflammatory Nrf2 signaling may represent a novel mechanism mediating the proatherogenic actions of saturated fatty acids.

KEYWORDS:

Human artery coronary smooth muscle cells; lipid-laden cells; migration; oxidation; proliferation

PMID:
30865473
DOI:
10.1152/ajpcell.00293.2018

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