Abstract
Neuropathological symptoms of Alzheimer's disease appear in advances stages, once neuronal damage arises. Nevertheless, recent studies demonstrate that in early asymptomatic stages, ß-amyloid peptide damages the cerebral microvasculature through mechanisms that involve an increase in reactive oxygen species and calcium, which induces necrosis and apoptosis of endothelial cells, leading to cerebrovascular dysfunction. The goal of our work is to study the potential preventive effect of the lipophilic antioxidant coenzyme Q (CoQ) against ß-amyloid-induced damage on human endothelial cells. We analyzed the protective effect of CoQ against Aβ-induced injury in human umbilical vein endothelial cells (HUVECs) using fluorescence and confocal microscopy, biochemical techniques and RMN-based metabolomics. Our results show that CoQ pretreatment of HUVECs delayed Aβ incorporation into the plasma membrane and mitochondria. Moreover, CoQ reduced the influx of extracellular Ca2+, and Ca2+ release from mitochondria due to opening the mitochondrial transition pore after β-amyloid administration, in addition to decreasing O2 .− and H2O2 levels. Pretreatment with CoQ also prevented ß-amyloid-induced HUVECs necrosis and apoptosis, restored their ability to proliferate, migrate and form tube-like structures in vitro, which is mirrored by a restoration of the cell metabolic profile to control levels. CoQ protected endothelial cells from Aβ-induced injury at physiological concentrations in human plasma after oral CoQ supplementation and thus could be a promising molecule to protect endothelial cells against amyloid angiopathy.
Highlights
Alzheimer disease (AD) is a chronic neurodegenerative pathology characterized by the proteolytic processing of the amyloid precursor protein to form amyloid peptide (Ab), which aggregates into extracellular amyloid plaques to cause neurotoxicity and the progressive cognitive decline typical of the disease in a process known as the ‘‘amyloid cascade’’ [1]
Increased O2.2 and H2O2 produced by dismutation of these radicals induces the opening of the permeability transition pore, a mitochondrial membrane channel involved in cell death, damaging mitochondria and inducing necrosis and apoptosis [16,17,18]
coenzyme Q (CoQ) prevents b-amyloid-induced endothelial cell death and restores migration and angiogenesis in vitro It was previously reported that cellular exposure to the amyloid fragment Ab25–35 results in endothelial cell toxicity similar to b1–42, via inducing cell apoptosis and necrosis [5]
Summary
Alzheimer disease (AD) is a chronic neurodegenerative pathology characterized by the proteolytic processing of the amyloid precursor protein to form amyloid peptide (Ab), which aggregates into extracellular amyloid plaques to cause neurotoxicity and the progressive cognitive decline typical of the disease in a process known as the ‘‘amyloid cascade’’ [1]. The concept of endothelial injury preceding neuronal damage is reinforced, first, by the fact that endothelial cells are the first line of contact with circulating Ab, second, by the observation that oxidative stress in cerebral blood vessels occurs when there is no evidence of Ab deposition in cerebral parenchyma and blood vessels, and third, by the observation that endothelial cells are more sensitive to Ab and its active fragment Ab25–35 than neurons or smooth muscle cells [2,5,6,7] Both Ab and Ab25–35, exert a prominent pro-apoptotic and necrotic effect on endothelial cells by mechanisms that involve an increase in free cytosolic calcium concentration ([Ca2+]i) and reactive oxygen species such as O2.2 and H2O2 [5,8,9,10,11]. This damage is further reinforced by trafficking and accumulation of the Ab peptide into mitochondrial cristae [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
