The effects of LC n-3 PUFA, EPA and OHA, on aspects of early stage atherosclerosis including monocyte to endothelial cell adhesion, monocyte to macrophage differentiation, and macrophage cholesterol levels, lipoprotein receptor, and lipid droplet-associated protein expression were investigated. LC n-3 PUFA treatment increased monocyte adhesion to endothelial monolayers and adhesion molecule expression (E-selectin; ICAM-1) in unstimulated HAECs with an opposite effect found in TNF-a stimulated HAECs (ICAM-1; VCAM-l). Adhesion was also decreased upon THP-1 monocyte incubation with LC n-3 PUFA, with no effect on expression of monocyte adhesion molecules. In monocyte to macrophage differentiation immature macro phages were affected at a lower L( n-3 PUFA concentration, and to a greater extent than mature macrophages. Upon L( n-3 PUFA treatment cell-surface expression of the differentiation markers CD11c, CD11b and CD49d on immature and mature macrophages, and (014 mRNA expression on mature macrophages were down- regulated, as was cell-surface expression of the scavenger receptor (036 in immature and mature macrophages, as well as (036 mRNA expression in immature The extent of macrophage differentiation influenced LC n-3 PUFA effects on cholesterol levels and lipoprotein expression. LC n-3 PUFA decreased net cholesterol levels in untreated, immature macrophages, and free cholesterol levels in native LDL treated, immature macro phages; mature macrophages were unaffected. LOX-l and LDLr mRNA expression were also decreased in immature macrophages. DHA increased adipophilin mRNA expression regardless of cell treatment. LC n-3 PUFA treatment during differentiation decreased CD36 cell-surface and mRNA expression in immature macrophages, and CD36 cell-surface and LOX-l mRNA expression in mature macrophages, whereas, post-differentiation treatment reduced LOX-l mRNA expression in immature macrophages with no effect on CD36 expression. LDLr mRNA expression was reduced with treatment during and post- differentiation. Treatment with the LC n-3 PUFA, EPA and DHA, can decrease monocyte adhesion to the endothelium, the expression of monocyte to macrophage differentiation markers, and cholesterol levels within differentiated macrophages.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:579794 |
| Date | January 2012 |
| Creators | McCartan, Sheila |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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