01whole.pdf (6.39 MB)
Download file

High blood pressure and cyclic stretch after cerebral amyloid deposition and endothelial function

Download (6.39 MB)
thesis
posted on 28.03.2022, 13:46 by Sumudu V. S. Gangoda
Background: Amyloid β (Aβ) deposition is a hallmark of Alzheimer’s disease (AD). Increased pulsatility, endothelial dysfunction (ED) and inflammation, indicators of vascular stiffness, are associated with AD. Additionally, vascular stiffness is linked to hypertension, a risk factor for AD. Aim: This study aimed to determine effects of high blood pressure (BP) on cerebral Aβ deposition in rodent models, spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) and investigate effects of cyclic stretch (CS) on expression of amyloid precursor protein (APP), endothelial nitric oxide synthase (eNOS) and intercellular cell adhesion molecule-1 (ICAM-1) in human cerebral microvascular endothelial cells (hCMEC). Methods: Hippocampal (HC) and frontal cortex (FC) regions of SHR and WKY rats were analysed using western blotting to determine effect of BP on cerebral Aβ deposition. hCMEC were subjected to 5%, 10% or 20 % CS compared to control (0% CS) to evaluate pulsatility, ED and inflammation using western blotting and/or RTqPCR. Results: Aβ oligomerisation increased in SHR compared to WKY in HC (P<0.01) and FC (P<0.001). APP mRNA expression increased at 5%, decreased at 20% CS; eNOS decreased at both (P<0.0001). APP and ICAM-1 protein expression dose-dependently increased at 5% and 10% CS (P<0.01) and decreased at 20% CS. eNOS protein levels decreased at all CS (P<0.0001). Conclusions: Results suggest that high BP and CS respectively alter the processing and expression of cerebral APP. Prolonged CS may induce ED by increasing ICAM-1, thereby mitigating eNOS expression. Findings mechanistically support the association of elevated pulsatility and arterial stiffness with AD.

History

Table of Contents

1. Introduction -- 2. Material and methods -- 3. Results -- 4. Discussion -- 5. Summary and conclusions.

Notes

Theoretical thesis. Bibliography: leaves 50-61

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

MRes, Macquarie University, Faculty of Human Sciences, Australian School of Advanced Medicine

Department, Centre or School

Australian School of Advanced Medicine

Year of Award

2014

Principal Supervisor

Alberto Avolio

Additional Supervisor 1

Mark Butlin

Additional Supervisor 2

Vivek K. Gupta

Rights

Copyright Sumudu VS Gangoda 2014. Copyright disclaimer: http://www.copyright.mq.edu.au

Language

English

Extent

1 online resource (xi, 61 leaves illustrations (some colour))

Former Identifiers

mq:42107 http://hdl.handle.net/1959.14/1050556