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• W4386251448 endingPage "C971" @default.
• W4386251448 startingPage "C951" @default.
• W4386251448 abstract "Endothelial integrity is critical in mitigating a vicious cascade of secondary injuries following acute ischemic stroke (AIS). Matrix metalloproteinase-9 (MMP-9), a contributor to endothelial integrity loss, is elevated during stroke and is associated with worsened stroke outcome. We investigated the FDA-approved selective sphingosine-1-phosphate receptor 1 (S1PR1) ligand, ozanimod, on the regulation/activity of MMP-9 as well as endothelial barrier components [platelet endothelial cell adhesion molecule 1 (PECAM-1), claudin-5, and zonula occludens 1 (ZO-1)] in human brain microvascular endothelial cells (HBMECs) following hypoxia plus glucose deprivation (HGD). We previously reported that S1PR1 activation improves HBMEC integrity; however, mechanisms underlying S1PR1 involvement in endothelial cell barrier integrity have not been clearly elucidated. We hypothesized that ozanimod would attenuate an HGD-induced increase in MMP-9 activity that would concomitantly attenuate the loss of integral barrier components. Male HBMECs were treated with ozanimod or vehicle and exposed to 3 h of normoxia (21% O2) or HGD (1% O2). Immunoblotting, zymography, qRT-PCR, and immunocytochemical labeling techniques assessed processes related to MMP-9 and barrier markers. We observed that HGD acutely increased MMP-9 activity and reduced claudin-5 and PECAM-1 levels, and ozanimod attenuated these responses. In situ analysis, via PROSPER, suggested that attenuation of MMP-9 activity may be a primary factor in maintaining these integral barrier proteins. We also observed that HGD increased intracellular mechanisms associated with augmented MMP-9 activation; however, ozanimod had no effect on these select factors. Thus, we conclude that ozanimod has the potential to attenuate HGD-mediated decreases in HBMEC integrity in part by decreasing MMP-9 activity as well as preserving barrier properties.NEW & NOTEWORTHY We have identified a potential novel mechanism by which ozanimod, a selective sphingosine-1-phosphate receptor 1 (S1PR1) agonist, attenuates hypoxia plus glucose deprivation (HGD)-induced matrix metalloproteinase-9 (MMP-9) activity and disruptions in integral human brain endothelial cell barrier proteins. Our results suggest that ischemic-like injury elicits increased MMP-9 activity and alterations of barrier integrity proteins in human brain microvascular endothelial cells (HBMECs) and that ozanimod via S1PR1 attenuates these HGD-induced responses, adding to its therapeutic potential in cerebrovascular protection during the acute phase of ischemic stroke." @default.
• W4386251448 created "2023-08-30" @default.
• W4386251448 creator A5014875412 @default.
• W4386251448 creator A5043430406 @default.
• W4386251448 date "2023-10-01" @default.
• W4386251448 modified "2023-10-03" @default.
• W4386251448 title "Ozanimod Differentially Preserves Human Cerebrovascular Endothelial Barrier Proteins and Attenuates MMP-9 Activity Following In Vitro Acute Ischemic Injury" @default.
• W4386251448 cites W10052869 @default.
• W4386251448 cites W107502543 @default.
• W4386251448 cites W1522014793 @default.
• W4386251448 cites W1545606956 @default.
• W4386251448 cites W1547601942 @default.
• W4386251448 cites W1849452095 @default.
• W4386251448 cites W1933215500 @default.
• W4386251448 cites W1955736456 @default.
• W4386251448 cites W1964570763 @default.
• W4386251448 cites W1965597112 @default.
• W4386251448 cites W1965785075 @default.
• W4386251448 cites W1965921916 @default.
• W4386251448 cites W1969788014 @default.
• W4386251448 cites W1973772667 @default.
• W4386251448 cites W1974618609 @default.
• W4386251448 cites W1977799997 @default.
• W4386251448 cites W1979590057 @default.
• W4386251448 cites W1979924329 @default.
• W4386251448 cites W1985230523 @default.
• W4386251448 cites W1986308117 @default.
• W4386251448 cites W1989979087 @default.
• W4386251448 cites W1991366770 @default.
• W4386251448 cites W1992912936 @default.
• W4386251448 cites W1994983033 @default.
• W4386251448 cites W1997360499 @default.
• W4386251448 cites W1997871462 @default.
• W4386251448 cites W1998641623 @default.
• W4386251448 cites W2000819485 @default.
• W4386251448 cites W2001349696 @default.
• W4386251448 cites W2008447781 @default.
• W4386251448 cites W2013821331 @default.
• W4386251448 cites W2013874197 @default.
• W4386251448 cites W2015585683 @default.
• W4386251448 cites W2016090496 @default.
• W4386251448 cites W2019486380 @default.
• W4386251448 cites W2020757356 @default.
• W4386251448 cites W2021114973 @default.
• W4386251448 cites W2021557435 @default.
• W4386251448 cites W2025688778 @default.
• W4386251448 cites W2028063897 @default.
• W4386251448 cites W2037434205 @default.
• W4386251448 cites W2037573897 @default.
• W4386251448 cites W2038561084 @default.
• W4386251448 cites W2039648938 @default.
• W4386251448 cites W2041601471 @default.
• W4386251448 cites W2043112660 @default.
• W4386251448 cites W2043982200 @default.
• W4386251448 cites W2048047884 @default.
• W4386251448 cites W2049760106 @default.
• W4386251448 cites W2064023379 @default.
• W4386251448 cites W2067935721 @default.
• W4386251448 cites W2069541617 @default.
• W4386251448 cites W2069634387 @default.
• W4386251448 cites W2069845573 @default.
• W4386251448 cites W2075060412 @default.
• W4386251448 cites W2076544464 @default.
• W4386251448 cites W2076690232 @default.
• W4386251448 cites W2079463602 @default.
• W4386251448 cites W2080600302 @default.
• W4386251448 cites W2081923855 @default.
• W4386251448 cites W2085493674 @default.
• W4386251448 cites W2089508958 @default.
• W4386251448 cites W2091002608 @default.
• W4386251448 cites W2104567497 @default.
• W4386251448 cites W2108147556 @default.
• W4386251448 cites W2109647778 @default.
• W4386251448 cites W2110656546 @default.
• W4386251448 cites W2112327424 @default.
• W4386251448 cites W2113892795 @default.
• W4386251448 cites W2121525722 @default.
• W4386251448 cites W2122866927 @default.
• W4386251448 cites W2125519677 @default.
• W4386251448 cites W2135174104 @default.
• W4386251448 cites W2135427416 @default.
• W4386251448 cites W2138897186 @default.
• W4386251448 cites W2139671059 @default.
• W4386251448 cites W2151299944 @default.
• W4386251448 cites W2154401382 @default.
• W4386251448 cites W2160985817 @default.
• W4386251448 cites W2164884787 @default.
• W4386251448 cites W2263570014 @default.
• W4386251448 cites W2264705762 @default.
• W4386251448 cites W2271212412 @default.
• W4386251448 cites W2295767781 @default.
• W4386251448 cites W2302006867 @default.
• W4386251448 cites W2509257484 @default.
• W4386251448 cites W2531824282 @default.
• W4386251448 cites W2552451940 @default.
• W4386251448 cites W2561851743 @default.
• W4386251448 cites W2567991959 @default.
• W4386251448 cites W2575375033 @default.

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