Effects of Regular and Consequent Citrus Fruit Consumption on Vascular Protection Specific Role of the Component Phytomicronutrients

Scientific context:

Arteriosclerosis is a chronic pathogenic inflammatory-fibro-proliferative process of large and medium-sized arteries that results in the progressive formation of fibrous plaques which in turn, impair the blood flow in vessels. These lesions can either promote an occlusive thrombosis in the affected artery (heart attack, thrombotic stroke) or produce a gradual but relentless stenosis of the arterial lumen. A number of subtle dysfunctions occur at the cellular and molecular levels in the early stages of disease progression associated with the loss of cellular homeostatic functions of endothelial cells, smooth muscle cells and macrophages which constitute the major cell types in the atheroma environment.

Several epidemiological studies shown a negative association between consumption of polyphenol-rich foods (fruits and vegetables) and CVD. This association has been partially explained by the fact that polyphenols interrupt lipid peroxidation which is implicated in the initiation of arteriosclerosis. Polyphenols contribution to the prevention of CVD could be attributable to their antioxidant capacity, hypolipidemic and/or anti-inflammatory properties as well as on their effects on metabolic pathways. Among fruits, citrus fruits are interesting sources of polyphenols (flavanones as glycosides) and carotenoids. A single glass of orange juice may contain between 40 and 140 mg flavanones, which may significantly contribute to the total daily polyphenol intake for the high citrus consumers. The clinical evidence of a role of citrus fruit consumption in the prevention of cardiovascular diseases concerns their hypocholesterolemic effect and the improvement of some biomarkers of oxidative stress, but the specific protective role of the phytomicronutrient provided by these beverages has never been considered. According to the type of citrus, the flavanone molecules are different: hesperetin in orange and clementine, naringenin in grapefruit and eriodyctiol in lemon. These molecules were shown to display antioxidant and hypolipidemic effects. Citrus also contains various carotenoids, like violaxanthin, lutein etc... as well as cryptoxanthin which acts as pro-vitamin A and has a positive role in CVD prevention. The specific health benefits brought by these phytomicronutrients are unknown and a clinical study with specific design to assess the contribution of citrus micronutrients has not been performed yet. Moreover, polyphenols and carotenoids are able to affect the expression of genes involved in atherogenesis. The interaction between these molecules on cellular responses is of particular interest. In fact, they could interplay in the cellular antioxidant network or directly (synergistically or antagonistically) affect gene expression. The unravellings of the mechanisms of regulation of transcriptional control of gene expression seems a promising future line of investigation. Newly developed high throughput technologies make a significant contribution to integrative biology. Studies on phytomicronutrients using the analysis of functional genomics and analysis of phenotypes by metabolic are still in its infancy. Integrated databases are necessary to understand their biological functions. The translation of basic scientific discoveries into applied nutrition is an increasing challenge.

Social and economic context:

CVD in adults are the main cause of morbidity and mortality in Western countries. In France, CVD are responsible for about 170 000 deaths a year i.e. 32% of all deaths, representing a total public heath expenditure estimated to 7.9%. As epidemiological studies show a protective effect of fruit and vegetable consumption towards CVD incidence, the National Programme for Nutrition and Health set up in France advices at least a 400g consumption of fruits and vegetable per day, equivalent to 5 items of crude or cooked fruits or vegetables. The present project will give a solid background for the understanding of the molecular mechanisms of the beneficial effects of polyphenols on human health.