Vascular Effects of Triglyceride-rich Lipoproteins

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Ingia / Ingia

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HaliImekamilika

Wadhamini

King's College London

Washirika

Royal Veterinary College

JARIBIO LA KLINIKI: NCT01618071

BioSeek: nct01618071

Maneno muhimu

Kikemikali

Many types of cardiovascular disease begin when the layer of cells lining blood vessels (endothelial cells) start to function abnormally. This causes white blood cells (monocytes) to enter the blood vessel wall and eventually form lesions. Fats from foods we consume are carried in the blood for 3-8 hours after a fatty meal in small particles known as chylomicrons (CM) and chylomicron remnants (CMR). The overall aim of this project is to investigate the idea that n-3 polyunsaturated fatty acids (PUFA) protect against heart disease by modifying the effect of CMR on endothelial cells and monocytes. We hypothesize that n3-PUFA carried in CMR reduce detrimental events which promote blood vessel damage and activate protective mechanisms to improve the function of arteries.

Tarehe

Imethibitishwa Mwisho:	08/31/2019
Iliyowasilishwa Kwanza:	06/07/2012
Uandikishaji uliokadiriwa Uliwasilishwa:	06/10/2012
Iliyotumwa Kwanza:	06/12/2012
Sasisho la Mwisho Liliwasilishwa:	09/11/2019
Sasisho la Mwisho Lilichapishwa:	09/15/2019
Tarehe halisi ya kuanza kwa masomo:	05/31/2012
Tarehe ya Kukamilisha Msingi iliyokadiriwa:	09/30/2012
Tarehe ya Kukamilisha Utafiti:	09/30/2012

Hali au ugonjwa

Postprandial Period

Lipemia

Vasodilation

Vascular Resistance

Nitric Oxide

Uingiliaji / matibabu

Dietary Supplement: High-fat meals varying in their fatty acid composition

Awamu

Vikundi vya Arm

Mkono	Uingiliaji / matibabu
Active Comparator: Oleic acid 75 g high oleic acid sunflower oil.
Active Comparator: Linoleic acid 75 g high linoleic acid sunflower oil.
Experimental: Eicosapentaenoic acid and docosahexaenoic acid 5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.
Experimental: Docosahexaenoic acid 5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.

Vigezo vya Kustahiki

Zama zinazostahiki Kujifunza	35 Years Kwa 35 Years
Jinsia Inastahiki Kujifunza	Male
Hupokea Wajitolea wa Afya	Ndio
Vigezo	Inclusion Criteria: - Healthy males - Non-smokers - Aged 35-70 years - Fasting TAG concentrations ≥1.2 mmol/L. Exclusion Criteria: - Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke), impaired fasting glucose/uncontrolled type 2 diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or bowel disease. - Presence of gastrointestinal disorder or use of drug, which is likely to alter gastrointestinal motility or nutrient absorption. - History of substance abuse or alcoholism (previous weekly alcohol intake >60 units/men) - Current self-reported weekly alcohol intake exceeding 28 units - Allergy or intolerance to any component of test meals - Unwilling to restrict consumption of any source of fish oil for the length of the study - Weight change of >3kg in preceding 2 months - Body Mass Index <20 and >35 kg/m2 - Fasting blood cholesterol > 7.8 mmol/L - Current cigarette smoker. - Current use of lipid lowering medication

Matokeo

Hatua za Matokeo ya Msingi

1. Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction [6 h post-meal]

The primary outcome of the study is activation of inflammatory/oxidative stress pathways within cultured endothelial cells following incubation with pooled postprandial lipoprotein fractions rich in chylomicron remnants. Due to the nature of this type of research this necessitates more than one primary outcome measure: the primary measures are NF-kappa-beta activation, cytokine production (e.g. interleukin-6) and reactive oxygen species generation in the cultured human endothelial cells.

Hatua za Matokeo ya Sekondari

1. Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol [0, 1, 2, 3, 4, 5 and 6 h post-meal]

2. Incremental area under the plasma concentration versus time curve (iAUC) of glucose [0, 1, 2, 3, 4, 5 and 6 h post-meal]

3. Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids [0, 1, 2, 3, 4, 5 and 6 h post-meal]

4. Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%) [0, 1, 2, 3, 4, 5 and 6 h post-meal]

5. Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol [0, 1, 2, 3, 4, 5 and 6 h post-meal]

6. Incremental area under the unit measure versus time curve for brachial augmentation index [0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal]

7. Incremental area under the unit measure versus time curve for systolic blood pressure [0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal]

8. Incremental area under the unit measure versus time curve for diastolic blood pressure [0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal]

9. Change in digital volume pulse stiffness index [0, 2, 4 and 6 h post-meal]

10. Change in digital volume pulse reflection index [0, 2, 4 and 6 h post-meal]

11. Change in plasma nitrite/nitrate concentrations [0, 2, 4 and 6 h]

12. Change in plasma 8-isoprostane F2alpha concentrations [0, 2, 4 and 6 h post-meal]

13. Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction [4 h post-meal]

14. Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction [5 h post-meal]