Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling

Authors

  • Lourdes M. Varela,

    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
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  • Beatriz Bermúdez,

    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
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  • Almudena Ortega-Gómez,

    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
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  • Sergio López,

    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
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  • Rosario Sánchez,

    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
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  • Jose Villar,

    1. Experimental Clinic Ward for Vascular Risk, IBIS, Virgen del Rocio University Hospital, CSIC, University of Seville, Seville, Spain
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  • Christelle Anguille,

    1. Center de Recherche en Biochimie Macromoléculaire, Centre National de la Recherche Scientifique (CNRS), Universite Mixte de Recherche 5237, Montpellier, France
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  • Francisco J. G. Muriana,

    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
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  • Pierre Roux,

    1. Center de Recherche en Biochimie Macromoléculaire, Centre National de la Recherche Scientifique (CNRS), Universite Mixte de Recherche 5237, Montpellier, France
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  • Rocío Abia

    Corresponding author
    1. Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain
    • Correspondence: Dr. Rocío Abia, Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa (CSIC), Avda. Padre García Tejero 4, 41012 Seville, Spain

      E-mail: abia@ig.csic.es

      Fax: + 34-954-616790

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Abstract

Scope

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.

Conclusion

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.

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