Donepezil prevents high glucose-induced endothelial barrier dysfunction and accelerates wound healing process in human coronary endothelial cells

Abstract The Cholinergic Anti-inflammatory Pathway (CAP) is a neurophysiological mechanism that regulates the immune system. Studies show CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in heart, lungs and gastrointestinal tract. Upon release, interacts with α7 nicotinic receptors (α7nAChR), down-regulate pro-inflammatory prevent tissue damage inflammation. Donepezil, centrally acting reversible acetylcholinesterase inhibitor, has been used palliative treatment Alzheimer’s disease (AD). We hypothesized donepezil prevents high glucose-induced endothelial barrier dysfunction accelerates wound healing process human coronary cells preventing destabilization junctional proteins. investigated potential protective role Donepezil glucose induced increase artery (HCAE) permeability process. Endothelial was evaluated using state art Electric Cell-substrate Impedance Sensing (ECIS) mechanism, measure trans-endothelial electrical resistance (TEER) across monolayers TEER electrodes. Wound assay performed employing electric signals to both monitor monolayer. Our data 25mM concentration increased abrogated at dose 5 μM 10 significantly prevented alteration function enhances presence concentration.