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

S. V. S. Gangoda, M. Butlin, Vivek Gupta, A. P. Avolio

    Research output: Contribution to journalMeeting abstract

    Abstract

    Background: Amyloid β (Aβ) deposition is a hallmark of Alzheimer’s disease (AD). Increased pulsatility, endothelial dysfunction (ED) and inflammation, as indicators of vascular stiffness, are associated with (AD). Additionally, vascular stiffness is linked to hypertension, a risk factor for AD. Aim: To determine effects of high blood pressure (BP) on cerebral Aβ deposition in the spontaneously hypertensive rat (SHR) and normotensive Wistar Kyoto (WKY) rat, and investigate effects of pulsatile 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. Methods: Hippocampal (HC) and frontal cortex (FC) regions of SHR and WKY rats were analysed using western blotting (WB) to determine effects 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 WB and/or quantitative RT-PCR. Results: Aβ oligomerization was increased in SHR compared to WKY in HC (P<0.01) and FC (P<0.001). APP mRNA level was increased at 5%, was decreased at 20%, while eNOS was decreased at both (P<0.0001). APP and ICAM-1 protein levels were dose-dependently increased at 5% and 10% CS (P<0.01) and decreased at 20% CS. eNOS protein levels were decreased at all CS (P<0.0001). Conclusions: Our 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.
    Original languageEnglish
    Pages (from-to)E35-E35
    Number of pages1
    JournalHypertension
    Volume65
    Issue number5
    Publication statusPublished - May 2015
    Event36th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) - Adelaide, Australia
    Duration: 26 Nov 201428 Nov 2014

    Cite this