Effect of azelnidipine on beta-amyloid peptide induced dysfunction of cerebral endothelial cells in vitro

Abstract

There is evidence that the receptor for advanced glycation endproducts (RAGE) is a binding site for amyloid β peptide (Aβ). RAGE is a multiligand cell surface receptor which is normally expressed in brain endothelium and, at low levels, in microglia and neurons. However, in Alzheimer's disease (AD) brains RAGE expression is increased by several-fold in cerebral endothelial cells (CECs), astrocytes, microglia, and neurons. Recent studies have demonstrated that RAGE is an important therapeutic target in AD. Therefore, there is a need to investigate new promising Aβ/RAGE axis blockers. It has been shown that azelnidipine (a highly lipid-soluble dihydropyridine-based calcium channel blocker) had a strong positive effect in RAGE-associated blood vessel damage in nondiabetic patients with stage I or II chronic kidney disease. In this study, we examined the effects of azelnidipine on A β 42 -induced activation of NADPH oxidase and consequent reactive oxygen species (ROS) generation, activation of NF-κB, ERK1/2 phosphorylation in CECs, and expression of P-selectin on the surface of the cells.