Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI.

Linmu Chen, Jun Zhang, Xiao Deng, Yan Liu, Xi Yang, Qiong Wu, Chao Yu

Biochemical and biophysical research communications 2017 Sep 23

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The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells. However, as the most active component of ox-LDL, there is no report showing whether LPA directly affects foam cell formation. The aim of this study was to investigate the effects of LPA on foam cell formation, as well as to elucidate the underlying mechanism. Oil red O staining and a Cholesterol/cholesteryl ester quantitation assay were used to evaluate foam cell formation in Raw264.7 macrophage cells. We utilized a Western blot and RT-PCR to investigate the relationship between LPA receptors and lipid transport related proteins. We found that LPA promoted foam cell formation, using 200 μM for 24 h. Meanwhile, the expression of the Scavenger receptor BI (SRBI), which promotes the efflux of free cholesterol, was decreased. Furthermore, the LPA1/3 receptor antagonist Ki16425 significantly abolished the LPA effects, indicating that LPA1/3 was involved in the foam cell formation and SRBI expression induced by LPA. Additionally, the LPA-induced foam cell formation was blocked with an AKT inhibitor. Our results suggest that LPA-enhanced foam cell formation is mediated by LPA1/3 -AKT activation and subsequent SRBI expression. Copyright © 2017. Published by Elsevier Inc.

Citation

Linmu Chen, Jun Zhang, Xiao Deng, Yan Liu, Xi Yang, Qiong Wu, Chao Yu. Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI. Biochemical and biophysical research communications. 2017 Sep 23;491(3):587-594