title: Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors.forename: Lourdes M
authors.initials: LM
authors.lastname: Varela
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bermúdez
authors.forename: Almudena
authors.initials: A
authors.lastname: Ortega-Gómez
authors.forename: Sergio
authors.initials: S
authors.lastname: López
authors.forename: Rosario
authors.initials: R
authors.lastname: Sánchez
authors.forename: Jose
authors.initials: J
authors.lastname: Villar
authors.forename: Christelle
authors.initials: C
authors.lastname: Anguille
authors.forename: Francisco J G
authors.initials: FJ
authors.lastname: Muriana
authors.forename: Pierre
authors.initials: P
authors.lastname: Roux
authors.forename: Rocío
authors.initials: R
authors.lastname: Abia
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003331:Coronary Vessels / Q000166:cytology*; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000008:administration & dosage; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D016014:Linear Models; D008074:Lipoproteins / Q000097:blood*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D008074:Lipoproteins; D012333:RNA, Messenger; D014280:Triglycerides; C030087:lipoprotein triglyceride; D019869:Phosphatidylinositol 3-Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: Atherosclerosis; Fatty acids; Human coronary artery smooth muscle cells; Invasion; Triglyceride-rich lipoproteins