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Title: The effects of n-3 long chain polyunsaturated fatty acids on THP-1 and endothelial cell function
Author: McCartan, Sheila
ISNI:       0000 0004 2742 6263
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available