Abstract

Introduction ECs from the microvascular bed modulate peripheral resistance and therefore are crucial for systemic blood pressure. Cardiovascular benefits of circulating phytochemicals require studying EC responses. Herein, we examined the acute effect of caffeic-related compounds on the ionic and redox responses in living ECs and, their relationship with their capacity to migrate, offering a mechanistic glance at the observed effects. Methods Isolated caffeic acid and its esters, neochlorogenic and CAPE, were diluted in DMSO. Real-time cytoplasmic Na+ and Ca2+ fluctuations were tracked in TIME cells (ATCC CRL-4025). The intracellular redox impact was assessed by tracking the fluorescence of HyPer biosensor, whereas H2O2 release was detected with Amplex Red kit. Finally, cellular migration capacity was evaluated by performing the wound assay. Results Only the phenethyl derivative of caffeic acid (CAPE) induced calcium responses in TIME cells at nanomolar concentrations, the extracellular source of such Ca2+ increases was supported by experiments without the divalent ion in the extracellular buffer. An increase in Na+ levels was also detected, suggesting the opening of a non-selective cationic permeability at the plasma membrane sensitive to CAPE. Incubation with this compound inhibited the migratory capacity of ECs, likely mediated by the inhibition of NADPH oxidase activity since no changes were observed in the intracellular redox state. Discussion Only CAPE is recognized at the plasma membrane by an entity that allows the influx of Ca2+ and Na+. TIME cells showed a diminished capacity to migrate, suggesting that CAPE modifies another cellular trait, likely the inhibition of NOX complex at the plasma membrane.