Cardiovascular Research Advance Access [Accepted Manuscript] published online on March 21, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn082
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The influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery
a Cellular and Molecular Nutrition, Instituto de la Grasa (CSIC), Seville, Spain
b Service of Internal Medicine, Hospitales Universitarios Virgen del Rocío, Seville, Spain
c Department of Functional Genome Analysis, German Cancer Research Center, Heidelberg, Germany
Corresponding author: Rocío Abia, Cellular and Molecular Nutrition, Instituto de la Grasa (CSIC), Avda. Padre García Tejero, 4, 41012 Seville, Spain. Tel: +34 954 611550; fax: +34 954 61679. E-mail address: abia{at}ig.csic.es
Aims: Postprandial triglyceride-rich lipoproteins (TRL) have a direct effect on vascular smooth muscle cells 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 smooth muscle cells (CASMC). In addition, the effect of TRL on cell proliferation and transcription factor activation was also evaluated.
Methods: 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.
Results: 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.
Time for primary review: 27 days
BB and SL contributed equally to this work.
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