Aβ-Induced Damage Memory in hCMEC/D3 Cells Mediated by Sirtuin-1

• Published in: International journal of molecular sciences Vol. 21; no. 21; p. 8226
• Main Authors: Liu, Haochen, Zhang, Yixuan, Zhang, Hong, Xu, Sheng, Zhao, Huimin, Liu, Xiaoquan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 03-11-2020; MDPI AG
• Subjects: Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer Disease - psychology; Alzheimer’s disease; Amyloid beta-Peptides - toxicity; Brain - blood supply; Brain - drug effects; Brain - metabolism; Brain - pathology; Carbazoles - pharmacology; Cells, Cultured; cerebrovascular endothelial damage memory; Endothelial Cells - drug effects; Endothelial Cells - physiology; Humans; kinetics process modeling; Memory - drug effects; Models, Theoretical; Plaque, Amyloid - complications; Plaque, Amyloid - metabolism; Plaque, Amyloid - physiopathology; Plaque, Amyloid - psychology; Reactive Oxygen Species - metabolism; sirt-1; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - physiology; vicious circle; kinetics process modeling; Alzheimer’s disease; cerebrovascular endothelial damage memory; sirt-1; vicious circle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21218226

It is well accepted by the scientific community that the accumulation of beta-amyloid (Aβ) may be involved in endothelial dysfunction during Alzheimer's disease (AD) progression; however, anti-Aβ anti-bodies, which remove Aβ plaques, do not improve cerebrovascular function in AD animal models. The reasons for these paradoxical results require investigation. We hypothesized that Aβ exposure may cause persistent damage to cerebral endothelial cells even after Aβ is removed (referred to as cerebrovascular endothelial damage memory). In this study, we aimed to investigate whether cerebrovascular endothelial damage memory exists in endothelial cells. hCMEC/D3 cells were treated with Aβ
for 12 h and then Aβ
was withdrawn for another 12 h incubation to investigate whether cerebrovascular endothelial damage memory exists in endothelial cells. A mechanism-based kinetics progression model was developed to investigate the dynamic characters of the cerebrovascular endothelial damage. After Aβ
was removed, the sirt-1 levels returned to normal but the cell vitality did not improve, which suggests that cerebrovascular endothelial damage memory may exist in endothelial cells. Sirt-1 activator SRT2104 and NAD
(Nicotinamide Adenine Dinucleotide) supplement may dose-dependently relieve the cerebrovascular endothelial damage memory. sirt-1 inhibitor EX527 may exacerbate the cerebrovascular endothelial damage memory. Kinetics analysis suggested that sirt-1 is involved in initiating the cerebrovascular endothelial damage memory; otherwise, NAD
exhaustion plays a vital role in maintaining the cerebrovascular endothelial damage memory. This study provides a novel feature of cerebrovascular endothelial damage induced by Aβ.