%0 Journal Article
%T Acetylcholinesterase Inhibitors Promote Angiogenesis in Chick Chorioallantoic Membrane and Inhibit Apoptosis of Endothelial Cells
%A Seyed Mohsen Mortazavian
%A Heydar Parsaee
%A Seyed Hadi Mousavi
%A Zahra Tayarani-Najaran
%A Ahmad Ghorbani
%A Hamid Reza Sadeghnia
%J International Journal of Alzheimer's Disease
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/121068
%X Alzheimer¡¯s disease (AD) is one of the most common causes of dementia in the elderly. Recently, a great attention has been paid to the possible role of vascular changes in the pathogenesis of AD. Reduced microvascular density and degeneration of the endothelium are of structural cerebrovascular changes in AD. Acetylcholinesterase (AChE) inhibitors are widely used for the improvement of AD symptoms. Until now, however, the effects of AChE inhibitors on vascular changes including angiogenesis and endothelial cell apoptosis are not fully understood. In the present work, the effects of three AChE inhibitors (donepezil, rivastigmine, and galantamine) were tested on H2O2-induced apoptosis in human umbilical vein endothelial cells (HUVECs) and on angiogenesis in chicken chorioallantoic membrane model. Incubation of HUVEC with H2O2 led to a significant decrease in cell viability and an increase in the percentage of apoptotic cells. The tested drugs, at concentrations of 1¨C100£¿¦ÌM, significantly inhibited the H2O2-induced toxicity. Also, all donepezil, rivastigmine and galantamine significantly increased the number of vessels in the chorioallantoic membrane when injected into fertilized eggs. In conclusion, AChE inhibitors possess angiogenesis-accelerating properties and have antiapoptotic effects on endothelial cells. These effects of AChE inhibitors may be involved in their beneficial effects on AD. 1. Introduction Alzheimer¡¯s disease (AD), a progressive neurodegenerative disorder, is the primary common cause of dementia in the elderly. Intracellular neurofibrillary tangles, amyloid plaques, neuronal loss, and vascular amyloidosis are of characteristic hallmarks of AD [1]. In spite of extensive studies, however, the molecular pathogenesis of AD is not yet fully understood. Some of the suggested mechanisms include amyloid-induced neurotoxicity, inflammatory reaction, oxidative stress, proteasome inhibitor-induced cell death, and cerebral hypoperfusion [2, 3]. Recently, a great attention has been paid to the possible role of vascular changes in the pathogenesis of AD [1, 2, 4, 5]. Vascular irregularities, reduced microvascular density, arteriolar and capillary atrophy, and degeneration of the endothelium are of structural cerebrovascular changes in AD [6, 7]. Death or dysfunction of endothelial cells leads to dysregulation of endothelial-neuronal-glial cell interactions and therefore contributes to the onset or progression of this disease. During AD, endothelial cells can be damaged by glia-derived cytokines, heavily aggregated proteins, and oxidative stress [8].
%U http://www.hindawi.com/journals/ijad/2013/121068/