{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:26:35Z","timestamp":1790195195344,"version":"4.1.0"},"reference-count":75,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Stroke is a leading global cause of human death and disability, with advanced aging associated with elevated incidences of stroke. Despite high mortality and morbidity of stroke, the mechanisms leading to blood\u2010brain barrier dysfunction and development of stroke with age are poorly understood. In the vasculature of brain, endothelial cells (ECs) constitute the core component of the blood\u2010brain barrier and provide a physical barrier composed of tight junctions, adherens junctions, and basement membrane.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We show, in mice, the incidents of intracerebral bleeding increases with age. After isolating an enriched population of cerebral ECs from murine brains at 2, 6, 12, 18, and 24\u2009months, we studied age\u2010associated changes in gene expression. The study reveals age\u2010dependent dysregulation of 1388 genes, including many involved in the maintenance of the blood\u2010brain barrier and vascular integrity. We also investigated age\u2010dependent changes on the levels of CpG methylation\u00a0and accessible chromatin in cerebral ECs. Our study reveals correlations between age\u2010dependent changes in chromatin structure and gene expression, whereas the dynamics of DNA methylation changes are different.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We find significant age\u2010dependent downregulation of the\n              <jats:italic>Aplnr<\/jats:italic>\n              gene along with age\u2010dependent reduction in chromatin accessibility of promoter region of the\n              <jats:italic>Aplnr<\/jats:italic>\n              gene in cerebral ECs.\n              <jats:italic>Aplnr<\/jats:italic>\n              is associated with positive regulation of vasodilation and is implicated in vascular health. Altogether, our data suggest a potential role of the apelinergic axis involving the ligand apelin and its receptor to be critical in maintenance of the blood\u2010brain barrier and vascular integrity.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.031044","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T10:36:28Z","timestamp":1692786988000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Age\u2010Associated Changes in Endothelial Transcriptome and Epigenetic Landscapes Correlate With Elevated Risk of Cerebral Microbleeds"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7978-5343","authenticated-orcid":false,"given":"Kshitij","family":"Mohan","sequence":"first","affiliation":[{"name":"Interfaculty Institute of Cell Biology University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"International Max Planck Research 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