P 252 - Oxidised lipids affect miR expression by microvascular endothelial cells

Abstract

Alzheimer's disease (AD) aetiology is complex with gene and environmental risk factor interaction. Our recent studies have confirmed that oxLDL is higher in vascular dementia patients and correlated with cognitive function. We hypothesised that endothelial cells of the blood-brain barrier are critical mediators of systemic nutrient effects within the brain. Therefore we have studied the effect of 27 hydroxycholesterol and F2alpha isoprostane on microvascular endothelial cell redox state, inflammatory cytokines and regulatory microRNA (miR) profile. We showed that lipids from patients with dementia or hypercholesterolaemia release directional inflammatory molecular signatures via an endothelial redox state-dependent mechanism. miR expression in endothelial cells with and without oxidised lipid treatment was undertaken using an Agilent DNA microarray scanner and microarray data was analysed using GeneSpring GX software. Upregulated miR showed an increase in oxidative stress and inflammatory pathways. Downregulated pathways included growth factor signalling. Using qPCR, we determined that miR-144 and 146 which are anti-inflammatory and redox regulating modulators were decreased by oxidised lipids. A neurotrophic factor-targeting miR was increased in expression. These data highlight that oxidised lipids have important regulatory effects on endothelial microvascular cell function.