Abstract 967: Coffee Consumption Increases Migratory Capacity and Mitochondrial Function of Endothelial Progenitor Cells and Mature Endothelial Cells
The assessment of a potential relation between coffee consumption and risk for coronary artery disease has provided controversial results in case-controlled and prospective cohort studies. Coffee consumption has been demonstrated to stimulate glucose metabolism. Thus, caffeine may influence mitochondrial energy metabolism, which was recently shown to be associated with migratory capacity of cells. Migratory capacity of endothelial cells (EC) is a key prerequisite for vascular repair following denuding injury or risk factor-mediated EC damage. Therefore, we hypothesized that there is a molecular link between caffeine, mitochondrial energy metabolism and EC migration. First, we measured migratory capacity and mitochondrial membrane potential (MP), which illustrates the capacity of mitochondria, of endothelial progenitor cells (EPC) isolated from healthy volunteers before and after 4 cups of coffee consumption. Migratory capacity and MP were significantly increased (migratory capacity before: 10.7 +/− 3.7, after: 20.3 +/− 7.4 cells/high power field p<0.001, n=8; MP before: 248.8 +/− 66.2, MP after: 321 +/− 47.6 JCI fluorescence geomean p<0.004, n=7, mean +/− SD). This was associated with an increase in blood-caffeine concentration from 4.2 +/− 3.2 μM to 22.5 +/− 6.5 μM caffeine. To get further insights into the molecular mechanisms, we incubated EPC and EC with 50 to 100 μM caffeine which did not increase intracellular calcium. Indeed, incubation with caffeine increased migratory capacity, MP and mitochondrial ATP biosynthesis of EPC and mature EC to a similar extent as the prototypical EC, promigratory stimulus VEGF (migratory capacity EC: 50 μM caffeine: 5.9 +/− 2.6 fold control, VEGF: 3.2 +/− 0.5 fold control). Inhibition of ATP synthase by oligomycin abrogated ATP biosynthesis and caffeine-induced migration. Moreover, depletion of mitochondria in EC completely blunted caffeine-induced migratory capacity, demonstrating that mitochondria are required for caffeine-induced migration. In conclusion, physiological concentrations of caffeine increase mitochondrial function and migratory capacity of endothelial progenitor and mature endothelial cells suggesting a protective effect for coffee consumption in coronary artery disease.