Azelnidipine Attenuates the Oxidative and NFκB Pathways in Amyloid-β-Stimulated Cerebral Endothelial Cells.

Cerebral amyloid angiopathy (CAA), a condition depicting cerebrovascular accumulation of amyloid β-peptide (Aβ), is a common pathological manifestation in Alzheimer's disease (AD). In this study, we investigated the effects of Azelnidipine (ALP), a dihydropyridine calcium channel blocker known for its treatment of hypertension, on oligomeric Aβ (oAβ)-induced calcium influx and its downstream pathway in immortalized mouse cerebral endothelial cells (bEND3). We found that ALP attenuated oAβ-induced calcium influx, superoxide anion production, and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and calcium-dependent cytosolic phospholipase A2 (cPLA2). Both ALP and cPLA2 inhibitor, methylarachidonyl fluorophosphate (MAFP), suppressed oAβ-induced translocation of NFκB p65 subunit to nuclei, suggesting that cPLA2 activation and calcium influx are essential for oAβ-induced NFκB activation. In sum, our results suggest that calcium channel blocker could be a potential therapeutic strategy for suppressing oxidative stress and inflammatory responses in Aβ-stimulated microvasculature in AD.