Title:Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro
Volume: 14
Issue: 7
Author(s): Mariateresa Cipriano, Giueseppe Esposito, Luana Negro, Elena Capoccia, Giovanni Sarnelli, Caterina Scuderi, Daniele De Filippis, Luca Steardo and Teresa Iuvone
Affiliation:
Keywords:
Angiogenesis, astrogliosis, palmitoylethanolamide.
Abstract: Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release of proinflammatory
and pro-oxidant mediators. Activated glial cells may release also pro-angiogenic molecules. The role of
angiogenesis in AD is still controversial: although angiogenesis brings oxygen and nutrients to injured tissue, it may also
exacerbate reactive gliosis. Moreover, by altering blood-brain barrier permeability pro-angiogenic mediators promote
passage of inflammatory/immune-competent cells into the brain, thereby exacerbating gliosis. The release of proangiogenic
factors during astrogliosis may thus be a key-step in controlling AD progression. The endogenous fatty acid
amide, palmitoylethanolamide (PEA), is a pleiotropic mediator exerting anti-inflammatory, antinociceptive and antiangiogenic
effects in several in vitro and in vivo models of chronic-degenerative disease. In this study, we investigated the
effects of PEA in AD angiogenesis and neuroinflammation by using conditioned medium from untreated and Aβ-treated
C6 rat astroglioma cells and HUVEC human endothelial cells. PEA (10-8-10-6 M) concentration-dependently reduced
expression of pro-inflammatory and pro-angiogenic markers in Aβ (1 μg/mL)-stimulated C6 cells. Moreover, culture
medium from PEA-treated C6 cells reduced HUVEC cell proliferation as compared to cells treated with conditioned
medium from Aβ-treated C6 cells. Immunocytochemical analysis revealed that PEA treatment inhibited nuclear levels of
mitogen-activated protein kinase 1 (the main pro-angiogenic pathway) and cytoplasmic vascular endothelial growth factor
in HUVEC cells receiving C6 conditioned medium. Finally, the peroxisome proliferator-activated receptor alpha inhibitor
GW6471, added to Aβ-treated C6 cells blocked all PEA effects in this model, suggesting that PEA acts through a
proliferator-activated receptor alpha-dependent mechanism on astroglial cells. Collectively, these data support the
potential therapeutic utility of PEA in AD.
