Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play an important role in the development and progression of proliferative cardiovascular diseases (CVDs), including hypertension, restenosis, and atherosclerosis [1–3].
Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and SMCs . PDGF is a dimeric molecule consisting of disulfide-bonded A and B-polypeptide chains. Homodimeric (PDGF-AA, PDGF-BB) as well as heterodimeric (PDGF-AB) isoforms exert their effects on target cells by binding with different specificities to two structurally related protein tyrosine kinase receptors, denoted α- and β-receptors [4, 5]. Abnormalities of PDGF receptor (PDGFR)/PDGF are thought to contribute to a number of human diseases, including malignancy and vascular diseases.
PDGF participates in stimulating SMC proliferation and migration during atherosclerosis . Expression of PDGF is low in normal blood vessels, but the levels of PDGF mRNA are increased following vascular smooth muscle cell transition into a synthetic state in culture  or after injury in vivo. PDGF and its cognate receptors are also expressed in tumors . PDGF stimulates autocrine growth of tumor cells and regulate tumor stromal fibroblasts and tumor angiogenesis . Overexpression of PDGF receptor and/or ligand is found in brain tumors and diverse malignancies.
In addition to PDGF, vascular injury also induces oxidative stress and elevated production of reactive oxygen species (ROS) in the vessel wall [11, 12]. Oxidative stress has been suggested to play an important role in the pathogenesis of CVDs, mainly through oxidative modification of low density lipoprotein, which initiates vascular inflammation and atherosclerotic lesion formation . The most important ROS for pathological conditions are superoxide (O2-) and hydrogen peroxide (H2O2). Inhibition of ROS reduces vessel remodeling and restenosis . Moreover, PDGFR activation increases intracellular ROS production and mediates PDGF signal transduction . It was reported that both PDGF and extracellular H2O2 at a higher concentration stimulation lead to intracellular ROS production and regulate protein tyrosine phosphatase (PTP), which induces an elevation of tyrosine-phosphorylated proteins [16–18].
Lutein and its stereo-isomer, zeaxanthin, are carotenoids without provitamin A activity and found in a wide variety of fruits and vegetables, including cooked spinach, lettuce, broccoli, peas, lima beans, orange juice, celery, string beans, and squash [19, 20]. It has been reported that higher quantities of dietary lutein were associated with lower risks of total stroke in the Health Professionals' Follow-Up Study . Moreover, two other key studies have provided support for a role of lutein and zeaxanthin in prevention of cardiovascular diseases, which shows inverse correlation of plasma lutein concentration and carotid intima-media thickness . In an in-vitro study, lutein and other carotenoids such as lycopene have been shown to reduce adhesion molecules expression in human aortic endothelial cells . This reflects a possible role of lutein in the prevention of atherosclerosis. Lutein exists in high concentration in the macula . However, dietary lutein stimulated delayed type hypersensitivity response, the number of CD4+ Th cells, and IgG production in dogs , suggesting its presence in peripheral areas and a possible protective role of lutein in vascular system.
We previously demonstrated that lycopene inhibits VSMC proliferation and migration through direct interaction with PDGF [25, 26]. The predominant carotenoids found in human plasma are lycopene, β-carotene, and lutein, and their concentrations vary from 0 to 8 μM depending upon dietary intake . In this study we evaluated lutein and its stereo isomer zeaxanthin on VSMC migration and PDGF signaling. Our results revealed a differential action mechanism of lutein from lycopene in inhibiting PDGF signaling and an opposite action of lutein and zeaxanthin on VSMC migration.