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

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 (nϭ6) or linoleic (nϭ7) 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 (PϽ0.001). The extent of in vitro LDL oxidation, measured by conjugated diene formation, was lower in the Greek subjects (PϽ0.02), 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 (PϽ0.001). There was an inverse correlation between the oleic acid content of LDL and stimulation of monocyte chemotaxis (rϭϪ0.64, PϽ0.001) 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 (rϭ0.51, PϽ0.01) 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 (PϽ0.001), 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 (PϽ0.001). There was a strong, negative correlation between oleic acid LDL content and monocyte adhesion (rϭϪ0.73, PϽ0.001) and a strong, positive correlation between polyunsaturated fatty acid LDL content and monocyte adhesion (rϭ0.87, PϽ0.001). This study demonstrates that dietary enrichment of LDL with oleic acid is realistic and readily achieved by using diets currently in use in Mediter...

Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: a randomized, crossover, controlled trial

“…LDL enriched in oleic acid promote less monocyte chemotaxis, compared with linoleic acid-enriched LDL, when exposed to oxidation (Tsimikas et al, 1999). Esposito et al (2004) found a reduction in the inflammatory markers after a 2-year follow-up of patients with metabolic syndrome consuming a Mediterranean-type diet.…”

Effect of phenol-rich extra virgin olive oil on markers of oxidation in healthy volunteers

“…In these studies, extra virgin olive oil vs high oleic acid sun¯ower oil or re®ned olive oil also did not affect the in vitro susceptibility of LDL to oxidation in fasting plasma samples. Other human studies on the effect of olive oil on LDL oxidation addressed the effects of oleic acid rather than olive oil phenols per se (Reaven et al, 1991;Bonanome et al, 1992;Tsimikas et al, 1999). In vitro, the olive oil phenols hydroxytyrosol and oleuropein strongly inhibited LDL oxidation (Visioli et al, 1995;Visioli & Galli, 1994).…”

Monounsaturated fatty acids and immune function

“…The authors suggest that the modulation of LDL fatty acid composition was responsible for the differences in adhesion and showed a significant negative correlation between monocyte adhesion to endothelial cells and the oleic acid content of LDL (Mata et al, 1996). Similarly, Tsimikas et al (1999) prepared and oxidized LDL from Greek and American subjects, with differing intakes of olive oil, and assessed monocyte chemotaxis induced by oxidised LDL. Induction of chemotaxis was 42% lower in Greeks compared to Americans and there was an inverse correlation between the OA content of LDL and monocyte chemotaxis, but a positive one between linoleic and AA and monocyte chemotaxis, suggesting that OA is anti-inflammatory and PUFA are pro-inflammatory (Tsimikas et al, 1999).…”

“…Similarly, Tsimikas et al (1999) prepared and oxidized LDL from Greek and American subjects, with differing intakes of olive oil, and assessed monocyte chemotaxis induced by oxidised LDL. Induction of chemotaxis was 42% lower in Greeks compared to Americans and there was an inverse correlation between the OA content of LDL and monocyte chemotaxis, but a positive one between linoleic and AA and monocyte chemotaxis, suggesting that OA is anti-inflammatory and PUFA are pro-inflammatory (Tsimikas et al, 1999).…”