{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:30:55Z","timestamp":1790818255539,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs\u2010derived exosomes in microglia polarization after stroke remains unknown. We isolated exosomes (Exos) from oxygen glucose deprivation (OGD)\u2010exposed HBMVECs, before added them into microglia. Microglia polarization markers were tested using RT\u2010qPCR or flow cytometry. Inflammatory cytokines were measured with ELISA. Endothelial cell damage was assessed by cell viability, apoptosis, apoptosis\u2010related proteins, oxidative stress, and angiogenic activity using CCK\u20108, flow cytometry, western blot, ELISA, and endothelial tube formation assay, respectively. We also established middle cerebral artery occlusion (MCAO) mice model to examine the function of circ_0000495 on stroke in\u00a0vivo. Our study found that HBMVECs\u2010Exos reduced M2 markers (IL\u201010, CD163, and CD206), increased M1 markers (TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u201012), CD86\u2010positive cells, and inflammatory cytokines (TNF\u2010\u03b1 and IL\u20101\u03b2), indicating the promotion of microglial M1\u2010polarization. Microglial M1\u2010polarization induced by HBMVECs\u2010Exos reduced viability and promoted apoptosis and oxidative stress, revealing the aggravation of endothelial cell damage. However, circ_0000495 silencing inhibited HBMVECs\u2010Exos\u2010induced alterations. Mechanistically, circ_0000495 adsorbed miR\u2010579\u20103p to upregulate toll\u2010like receptor 4 (TLR4) in microglia; miR\u2010579\u20103p suppressed HBMVECs\u2010Exos\u2010induced alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated circ_0000495 in HBMVECs. Importantly, circ_0000495 aggravated ischemic brain injury in\u00a0vivo via activating TLR4\/nuclear factor\u2010\u03baB (NF\u2010\u03baB) pathway. Collectively, OGD\u2010treated HBMVECs\u2010Exos transmitted circ_0000495 to regulate miR\u2010579\u20103p\/TLR4\/NF\u2010\u03baB axis in microglia, thereby facilitating microglial M1\u2010polarization and endothelial cell damage.<\/jats:p>","DOI":"10.1096\/fj.202301637r","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T08:19:05Z","timestamp":1704788345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Brain microvascular endothelial cell\u2010derived exosomes transmitting circ_0000495 promote microglial\n                    <scp>M1<\/scp>\n                    \u2010polarization and endothelial cell injury under hypoxia condition"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-1541","authenticated-orcid":false,"given":"Xiao\u2010li","family":"Min","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Diseases The 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