Interestingly, both orange juice and hesperidin induced expression of BCL6, a transcriptional repressor that prevents the expression of CD80 by binding to its promoter region. Furthermore, orange juice and hesperidin also induced the expression of FG-4592 another cell adhesion molecule, CEACAM3 which inactivation induced neutrophil adhesion to endothelial cells. The transcriptome study also revealed the downregulation of ITGBL1 by both orange juice and hesperidin, while only orange juice decreased the expression of several other genes encoding integrins, such as ITGA5, ITGA7 and ITGAX. It has been shown that ITGAX deficiency reduced the firm arrest of monocytes on vascular cells, monocyte/macrophage accumulation in intimae and consequently, reduced atherosclerosis development inapoE2/2 mice fed a high-fat diet. Besides the observed modification in expression of the integrin genes, we also observed expression modulation of genes encoding connexins, known as gap junction adhesion molecules. For example, both orange juice and hesperidin downregulated the expression of connexin 31.3 while connexins 30, 40 and 46 were only downregulated by orange juice. In response to orange juice or hesperidin consumption, the combined expression regulation of genes encoding chemokines and their receptors and adhesion molecules suggests a lower recruitment and infiltration of circulating cells to the vascular wall. From our study, a large subset of genes implicated in the processes of lipid metabolism and transport has been identified as differentially expressed in response to orange juice and hesperidin consumption. In particular, we observed a significant downregulation of LDLR, the receptor responsible for LDL binding and internalization in macrophages. Inside the cell, free cholesterol is converted to a cholesteryl ester and forms lipid droplets due to acylCoA:cholesterol acyltransferase activity. In our study, ACAT2 was downregulated by orange juice consumption, suggesting a potential decrease in lipid droplet accumulation, which could reduce foam cell formation. This result could be in agreement with a previous study which showed that flavonoid from grapefruit, naringenin, inhibits ACAT2 activity. Furthermore, macrophage intracellular cholesterol is regulated by membrane transporters of the ATP-binding cassette superfamily. These proteins are implicated in reverse cholesterol transport from macrophages, which represents a potential protective effect against foam cell formation, the hallmark of atherosclerosis. ABCA2 is one of the most upregulated genes by both orange juice and hesperidin. Moreover, both orange juice and hesperidin also induced expression of the ABCF1 gene, while orange juice up-regulated other ABC-transporter genes, such as ABCG1 and ABCB5. Disrupting ABCG1 in mice was observed to promote the accumulation of excess cholesterol in macrophages. Overall, the observed decrease in the expression of genes encoding the LDL receptor and ACAT2 together with an increase in the expression of genes regulating reverse cholesterol transport suggests that white blood cells would be less prone to differentiate into foam cells after 4 weeks of orange juice or hesperidin consumption.