[OP.2D.03] PULSATILE STRETCH ALTERS EXPRESSION AND PROCESSING OF AMYLOID PRECURSOR PROTEIN IN HUMAN CEREBRAL ENDOTHELIAL CELLS

Autor: Vivek Gupta, Roger S. Chung, Sumudu V. S. Gangoda, Alberto Avolio, Mark Butlin
Rok vydání: 2016
Předmět:
Zdroj: Journal of Hypertension. 34:e24
ISSN: 0263-6352
DOI: 10.1097/01.hjh.0000491393.79855.fc
Popis: Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Aβ is generated via enzymatic cleavage of amyloid precursor protein (APP). Increased APP expression is associated with elevated amyloid burden. Elevated pulsatility of arterial pressure, as a vascular factor indicative of vascular stiffness, is associated with AD. This study investigates whether increased magnitude of pulsatile stretch of human cerebral microvascular endothelial cells (hCMEC) alters expression and processing of APP.hCMECs were cultured on flexible silicone chambers and subjected to 5%, 10% or 15% cyclic stretch (ShellPA stretch system, Menicon Life Science) for 18 hours at 1 Hz (n = 5-11 for each stretch magnitude). Comparison was made with controls (0% stretch) to evaluate the effect of pulsatility on APP. APP expression was quantified using western blots with glyceraldehyde 3-phosphate dehydrogenase as the loading control. APP processing was evaluated in the cell culture supernatants by ELISA for secreted Aβ42. Results were analyzed using one way ANOVA (mean ± SEM, % control) or Pearson correlation.The densitometric analysis (expressed as a percentage of control values) of protein expression of APP showed that it was significantly higher at 10% of cyclic stretch (160.9 ± 21%) compared to both the static control (100%, p
Databáze: OpenAIRE