Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling
Article first published online: 24 FEB 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 6, pages 1349–1364, June 2014
How to Cite
Varela, L. M., Bermúdez, B., Ortega-Gómez, A., López, S., Sánchez, R., Villar, J., Anguille, C., Muriana, F. J. G., Roux, P. and Abia, R. (2014), Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling. Mol. Nutr. Food Res., 58: 1349–1364. doi: 10.1002/mnfr.201300749
- Issue published online: 5 JUN 2014
- Article first published online: 24 FEB 2014
- Manuscript Accepted: 22 JAN 2014
- Manuscript Revised: 3 JAN 2014
- Manuscript Received: 10 OCT 2013
- Spanish Ministry of Science and Innovation (MICINN). Grant Numbers: AGL2008-02811, AGL2011-29008
- European Commission (EC) Marie Curie. Grant Number: PERG07-GA-2010–268413
- Fatty acids;
- Human coronary artery smooth muscle cells;
- Triglyceride-rich lipoproteins
The aim was to investigate the effect of postprandial triglyceride-rich lipoproteins (TRLs) with different fatty acid compositions on human coronary artery smooth muscle cell (hCASMC) invasion and to identify the molecular pathways involved.
Methods and results
TRLs were isolated from the plasma of healthy volunteers after the ingestion of single meals enriched in MUFAs, saturated fatty acids (SFAs), or PUFAs. hCASMC invasion was analyzed using transwell chambers with Matrigel. TRLs–SFAs provoked the highest invasion, followed by TRLs–MUFAs and TRLs–PUFAs. Inhibition studies with Orlistat showed that invasion was dependent on the fatty acid composition of the TRLs. Fatty acids incorporated into the cell membranes strongly associated with cell invasion. Pull-down assays showed that TRLs–SFAs were able to increase Rac1 activity via inhibition of RhoA-dependent signaling. Chemical inhibition and siRNA studies showed that Rac1, PI3k, JNK, and MMP2 regulates TRL–SFA-induced hCASMC invasion.
We demonstrate for the first time that TRLs induce hCASMCs invasion in a fatty acid dependent manner. This effect in TRLs–SFAs is mediated by the PI3k-Rac1-JNK, RhoA, and Rac1-MMP2 pathways. The ingestion of MUFA, compared to other dietary fatty acids such as SFA, could be considered as a nutritional strategy to reduce the atherosclerotic plaque formation.