ENDOMED · Characterizing the effects of the Mediterannean diet on endothelial dysfunction
FP7 — People (Marie Curie Actions)
- Duration
- 2009-06-01 → 2011-05-31
- EU contribution
- €161,162
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
Characterizing the effects of the Mediterranean diet on endothelial dysfunction
Postprandial metabolism raises as a main factor for developing inflammation related diseases. Glucose homeostasis, thrombosis or fibrinolysis balance and lipoprotein metabolism are features of the postprandial metabolism that can be changed by the type of diet, and particularly by the type of consumed fat. It was recently discovered by our group that dietary fat could even influence gene expression in Peripheral blood mononuclear cells (PBMCs), inducing different gene expression profiles depending on the type of consumed fat. These gene expression changes were the result of the combination of the direct and indirect effects of the fatty acids on the PBMCs, the different tissues and organs that released several hormones and cytokines as a response to the impact induced by the consumed fat. Whether these gene expression changes are in fact translated to protein is not known yet; however previous studies pointed to an increased adhesion capacity to the endothelial cells after the consumption of a high fat meal, therefore promoting intravascular infiltration of the PBMCs. Following these preliminary results we considered that pathways of the transcription factors NF-?B and PPARa, plus the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, might be differently up-regulated by the distinct types of dietary fat. IL1B is a potent pro-inflammatory cytokine that is secreted by macrophages in the adipose tissue of type-II diabetic patients and its transcription is regulated by the nuclear transcription factor ?B (NF-?B) activity. Moreover, PDK4 is a known PPARa target gene and NCF4 is a cytosolic regulatory member of the NADPH oxidase complex, which is responsible of the production of superoxide anion within the cells. The up-regulation of these genes suggested that Polyunsaturated fatty acids (PUFA) and Mono-unsaturated fatty acid (MUFA) might be able to induce a postprandial pro-inflammatory response prior to an increase in Reactive oxygen species (ROS) production. Moreover, in response to the fat intake, the Peroxisome proliferator-activated receptor alpha (PPARa) was up-regulated as well and proved to be sensible to polyunsaturated and monounsaturated fatty acids. Along the course of the ENDOMED project we also examined whether these pathways were fully activated during in vivo monocytes from lean healthy and obese healthy subjects via the measurement of other genes related to inflammation, lipid metabolism and oxidative stress pathways. These studies were anticipated to reveal whether distinct dietary fats induced different gene expression changes, thus providing some information for future nutritional advice and for reducing the development of inflammation related diseases, such as type-II diabetes or cardiovascular diseases.
Data: CORDIS, © European Union
Project objective
It is well established that death rates from cardiovascular disease are substantially lower in Mediterranean countries, which has been attributed the consumption of an unique collection of foods referred to as the Mediterranean diet. Although the mechanisms underlying the effects of the Mediterranean diet on cardiovascular disease remain largely unclear, a important role for polyphenols and monounsaturated fatty acids, which are abundantly present in olive oil, is suspected. Endothelial dysfunction is a hallmark for the initial stage of vascular dysfunction and has been associated with cardiovascular disease. Consumption of high fat meals result in an impaired postprandial endothelial function as measured by flow-mediated dilatation, markers of inflammation and markers of oxidative stress. However, the mechanism that mediate the effects of high fat meals on endothelial function remains unclear. The aim of the present project is to uncover the mechanisms that underlie the preventive effects of the Mediterranean diet on development of cardiovascular diseases, with a focus on endothelial dysfunction and the specific impact of monounsaturated fatty acids and polyphenols. To that end, we will perform whole genome expression profiling on Peripheral Blood Mononuclear Cells collected from 20 healthy young Caucasian men that received a milkshake containing 55 grams of SFA enriched or MUFA enriched fat as part of a single-blind cross-over dietary intervention trial. In addition, we will expose freshly isolated HUVEC and PBMC with specific dietary fatty acids and polyphenols for analysis of gene expression and protein secretion of specific markers of endothelial activation, inflammation, and oxidative stress. Characterizing the activity and mechanism of action of these dietary components may lead to the identification of valuable new targets in the prevention of cardiovascular diseases.
Original text from CORDIS.
Participants
- WAGENINGEN UNIVERSITY · WageningenCoordinatorNetherlands
Links
Data: CORDIS, © European Union