title: LDL isolated from Greek subjects on a typical diet or from American subjects on an oleate-supplemented diet induces less monocyte chemotaxis and adhesion when exposed to oxidative stress.
abstract: The mechanisms underlying the cardiovascular benefits of Mediterranean-style diets are not fully understood. The high content of monounsaturated fatty acids in Mediterranean-style diets derived from oleate-rich olive oil may be beneficial in reducing low density lipoprotein (LDL) oxidation and its subsequent development of atherogenic properties. This study sought to assess the proinflammatory potential of LDL isolated from subjects consuming a diet naturally rich in olive oil. LDL was isolated from 18 Greek, 18 American, and 11 Greek-Americans subjects, all of whom were living in the United States. Fatty acid composition and vitamin E levels of LDL were determined, as was the extent of copper-mediated LDL oxidation. LDL was also mildly oxidized by exposure to fibroblasts overexpressing 15-lipoxygenase and tested in vitro for bioactivity by determining its ability to stimulate monocyte chemotaxis and adhesion to endothelial cells. To confirm that dietary fatty acids influence the proinflammatory properties of mildly oxidized LDL, LDL was also isolated from 13 healthy American subjects after consumption of an 8-week liquid diet supplemented with either oleic (n=6) or linoleic (n=7) acid and tested for bioactivity in a similar fashion. There were no differences in the baseline lipid profiles among the Greeks, Americans, or Greek-Americans. Oleic acid content in LDL was 20% higher in the Greek compared with the American or Greek-American subjects (P<0.001). The extent of in vitro LDL oxidation, measured by conjugated diene formation, was lower in the Greek subjects (P<0.02), but there was no difference in the lag time. Induction of monocyte chemotaxis and adhesion by mildly oxidized LDL was decreased by 42% in the Greek group compared with the American subjects (P<0.001). There was an inverse correlation between the oleic acid content of LDL and stimulation of monocyte chemotaxis (r=-0.64, P<0.001) and a positive correlation between the polyunsaturated fatty acid content of LDL (total linoleate and arachidonic acids levels in LDL) and stimulation of monocyte chemotaxis (r=0.51, P<0.01) in the entire cohort. There were no differences in LDL vitamin E content between the groups. In the liquid-diet groups, the oleic acid-supplemented group had a 113% higher oleic acid content in LDL and a 46% lower linoleic acid content in LDL than the linoleate-supplemented group (P<0.001), whereas the vitamin E content in LDL was equal in both groups. When exposed to oxidative stress, the LDL enriched in oleic acid promoted less monocyte chemotaxis (52% lower) and reduced monocyte adhesion by 77% in comparison with linoleate-enriched LDL (P<0.001). There was a strong, negative correlation between oleic acid LDL content and monocyte adhesion (r=-0.73, P<0.001) and a strong, positive correlation between polyunsaturated fatty acid LDL content and monocyte adhesion (r=0.87, P<0.001). This study demonstrates that dietary enrichment of LDL with oleic acid is realistic and readily achieved by using diets currently in use in Mediterranean countries. In addition, these data suggest that LDL enriched with oleic acid and reduced in polyunsaturated fatty acids may be less easily converted to a proinflammatory, minimally modified LDL.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of California at San Diego, La Jolla, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tsimikas
authors.forename: A
authors.initials: A
authors.lastname: Philis-Tsimikas
authors.forename: S
authors.initials: S
authors.lastname: Alexopoulos
authors.forename: F
authors.initials: F
authors.lastname: Sigari
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: P D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D006115:Greece / Q000208:ethnology; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D019301:Oleic Acid / Q000097:blood; D009829:Oleic Acids / Q000008:administration & dosage*; D000069463:Olive Oil; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010938:Plant Oils / Q000032:analysis; D014481:United States; D014810:Vitamin E / Q000097:blood
chemical_list: D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D000069463:Olive Oil; D010938:Plant Oils; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D019301:Oleic Acid; D019787:Linoleic Acid