Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery.
OBJECTIVE
Postprandial triglyceride-rich lipoproteins (TRL) have a direct effect on vascular smooth muscle cells (SMC) and they increase the risk of atherogenesis. Here, we have tested the hypothesis that the different fatty acid composition of TRL is capable of differentially modifying gene expression in human coronary artery SMC (CASMC). In addition, the effect of TRL on cell proliferation and transcription factor activation was also evaluated.


RESULTS
TRL were prepared from plasma of healthy volunteers after the ingestion of meals enriched in refined olive oil (ROO), butter or a mixture of vegetable and fish oils (VEFO). We use cDNA microarrays to determine the genes differentially expressed in TRL-treated CASMC. Correspondence cluster analysis demonstrated that TRL-butter, -ROO and -VEFO provoked different transcriptional profiles in CASMC. Sixty-six genes were regulated by TRL-butter, 55 by -ROO, and 47 by -VEFO. The data revealed that TRL-butter predominantly activated genes involved in the regulation of cell proliferation and inflammation. Likewise, TRL-VEFO induced the expression of genes implicated in inflammation, while TRL-ROO promoted a less atherogenic gene profile.


CONCLUSIONS
The pathophysiological contribution of TRL to the development of atherosclerosis and the stability of atherosclerotic plaques may depend on the fatty acid composition of TRL. Our findings suggest a role for macrophage-inhibiting cytokine-1 (MIC-1) in coronary artery cardiovascular events.
Bermúdez
Beatriz
B
Cellular and Molecular Nutrition, Instituto de la Grasa, Avda, Padre García Tejero, 4, 41012 Seville, Spain.
López
Sergio
S
Pacheco
Yolanda M
YM
Villar
José
J
Muriana
Francisco J G
FJ
Hoheisel
Jöerg D
JD
Bauer
Andrea
A
Abia
Rocío
R
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016000:Cluster Analysis; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D055436:Growth Differentiation Factor 15; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D019518:Postprandial Period / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism* / Q000494:pharmacology
D016207:Cytokines; D005227:Fatty Acids; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014280:Triglycerides