Autor: |
Moss JWE; Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. Ramji@Cardiff.ac.uk., Williams JO; Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. Ramji@Cardiff.ac.uk., Al-Ahmadi W; Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. Ramji@Cardiff.ac.uk., O'Morain V; Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. Ramji@Cardiff.ac.uk., Chan YH; Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. Ramji@Cardiff.ac.uk., Hughes TR; Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK., Menendez-Gonzalez JB; European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK., Almotiri A; European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK., Plummer SF; Cultech Limited, Unit 2 Christchurch Road, Baglan Industrial Park, Port Talbot, SA12 7BZ, UK., Rodrigues NP; European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK., Michael DR; Cultech Limited, Unit 2 Christchurch Road, Baglan Industrial Park, Port Talbot, SA12 7BZ, UK., Ramji DP; Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. Ramji@Cardiff.ac.uk. |
Abstrakt: |
Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3 polyunsaturated fatty acids, flavanols and phytosterols has many beneficial effects on cardiovascular disease. However, their combined actions on the risk factors for atherosclerosis remains poorly understood. We have previously shown that a formulation containing each of these active components at physiologically relevant doses modulated several monocyte/macrophage processes associated with atherosclerosis in vitro, including inhibition of cytokine-induced pro-inflammatory gene expression, chemokine-driven monocyte migration, expression of M1 phenotype markers, and promotion of cholesterol efflux. The objectives of the present study were to investigate whether the protective actions of the formulation extended in vivo and to delineate the potential underlying mechanisms. The formulation produced several favourable changes, including higher plasma levels of HDL and reduced levels of macrophages and myeloid-derived suppressor cells in the bone marrow. The mRNA expression of liver-X-receptor-α, peroxisome proliferator-activated receptor-γ and superoxide dismutase-1 was induced in the liver and that of interferon-γ and the chemokine (C-X-C motif) ligand 1 decreased, thereby suggesting the potential mechanisms for many beneficial effects. Other changes were also observed such as increased plasma levels of triglycerides and lipid peroxidation that may reflect potential activation of brown fat. This study provides new insights into the protective actions and the potential underlying mechanisms of the formulation in vivo, particularly in relation to risk factors together with changes in systemic inflammation and hepatic lipid alterations associated with atherosclerosis and metabolic syndrome, and supports further assessments in human trials. |