title: Starvation triggers Abeta42 generation from human umbilical vascular endothelial cells.
abstract: Cerebral amyloid angiopathy is a common feature in Alzheimer's disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce Abeta(42) under starvation. Starvation can increase the secretion of Abeta(42) by altering the expression of beta-secretases (BACE1) and gamma-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of Abeta(42) produced under starvation in HUVECs. These results suggest that starvation-induced Abeta(42) secretion might contribute to the formation of CAA and hence vascular degeneration in AD.
authors.affiliation: Department of Neurology & Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Ma
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qiang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Xin
authors.forename: Hui-Dong
authors.initials: HD
authors.lastname: Tang
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ding
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013217:Starvation / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism; D014472:Umbilicus
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D053829:Amyloid Precursor Protein Secretases