Full Title: Serum from patients affected by Alzheimer disease shows a paraoxonase-dependent pro-apoptotic effect on endothelial cells
Journal: Free Radical Biology and Medicine
Year of Publication: 2017
Publication Author(s): Ilaria Crivellari, Carlo Cervellati, Francesco Vieceli Dalla Sega, Giuseppe Valacchi, Alessandro Trentini, Angelina Passaro, Cristina Bosi, Arianna Romani, Fabrizio Franzè, Carla Resca, Francesca Fortini, Giovanni Zuliani, Paola Rizzo
High-density lipoprotein (HDL) protects, among others, endothelial cells from oxidative challenge. The functionality of HDL closely depends on enzymes such as paraoxonase-1(PON-1), PAF-AH and myeloperoxidase (MPO). Decreased activities of these enzymes have been found in association with higher risk of endothelial dysfunction (ED). Growing evidence suggests that this vascular abnormality is implicated in Alzheimer’s disease (AD) development. We have recently shown that decreased PON-1 is an early event in AD development. However, the mechanism underlying the axis HDL dysfunction-ED-AD has not been proved yet. Since it is now clear that endothelial apoptosis is one of the hallmarks of ED, we sought to determine whether serum from AD patients affects this death process in human umbilical vein endothelial cells (HUVEC). Sera of 10 patients (n=4 controls, n=6 AD) were assessed for MPO, PON-1 and incubated for 48 h with HUVEC. Apoptosis levels were assessed with the Annexin V-FITC binding assay (flow cytofluorimetry). AD patients had 42 and 10% lower levels of PON-1, PAF-AH, respectively and 39% higher MPO than controls. Regarding in vitro assay, cells treated with AD serum presented a significant (p<0.05) increase of (mostly early) apoptosis compared to controls. Our findings suggest that dysfunctional HDL-driven endothelial apoptosis may be implicated in AD pathogenesis.
Link to Article: https://www.sciencedirect.com/science/article/pii/S0891584917305075