Age-associated changes in endothelial transcriptome and chromatin landscape correlate with elevated risk of hemorrhage

• DOI: 10.1101/2023.02.10.528012
• Publication Date: 2023-02-11T05:20:15Z
• Authors: Kshitij Mohan; Gilles Gasparoni; Abdulrahman Salhab; Michael M. Orlich; Robert Geffers; Steve Hoffmann; Ralf H. Adams; Jörn Walter; Alfred Nordheim
• Keywords: Adherens junction

Abstract Intracerebral hemorrhage (ICH), a devastating form of stroke, is leading global cause human death and disability. The major risk factors for ICH include increasing age, hypertension cerebral amyloid angiopathy. Despite high mortality morbidity associated with ICH, the mechanisms to blood-brain barrier (BBB) dysfunction age development hemorrhagic stroke poorly understood. In vasculature central nervous system, endothelial cells (ECs) constitute core component BBB provide physical due tight junctions, adherens basement membrane layers. this study, we show in brains mice that incidents intracerebral bleeding increase advancing age. After isolation an enriched population ECs, studied gene expression ECs isolated from murine ages 2, 6, 12, 18, 24 months. study reveals agedependent dysregulation 1388 genes including many involved maintenance vascular integrity. Since epigenetic regulate expression, also investigated age-dependent changes at levels CpG methylation accessible chromatin ECs. Our correlations between structure expression. We find significant downregulation apelin receptor ( Aplnr ) along reduction accessibility promoter gene. known play crucial role positive regulation vasodilation implicated health. Interestingly, observe protein brain, potentially implicating be critical increased ageing.