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Abstract:
Intracerebral hemorrhage (ICH) is associated with disruption of the blood-brain barrier and rupture of blood vessels, leading to the leakage of blood into brain tissues. The major risk factors for ICH are old age, hypertension and cerebral amyloid angiopathy. Weinl et al. (2015) have previously established in murine knock-out models that postnatal and adult endothelial cell (EC)-specific down-regulation of the transcription factor SRF, or its cofactors MRTF-A and MRTF-B, leads to impaired cerebral vessel integrity, resulting in microbleeds and larger hemorrhages in mouse brains. My preliminary studies in mice demonstrated increased incidents of bleeding in brain with increasing age. RNA-seq data from the ECs of aging mice show differential expression of crucial genes responsible for the organization and maintenance of the blood-brain barrier and vascular integrity. We further hypothesize that the differential expression of genes in the cerebral ECs of aging mice may be attributed to epigenetics, and hence underlying epigenetic control mechanisms in ageing mice have been investigated at the level of chromosomal CpG methylation by RRBS (Reduced Representation Bisulfite Sequencing), and at the level of chromatin structure by ATAC-seq (Assay for Transposase-Accessible Chromatin Sequencing). This study on ageing mice promises to provide insights into potential molecular causes of age-dependent hemorrhagic stroke and small vessel disease in elderly human patients.
