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• W2962506670 abstract "BackgroundVascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood.ObjectivesTo explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoagulable mice.MethodsFactor VIII (FVIII)‐deficient mice +/− FVIII treatment and hypocoagulable wild‐type mice (HypoBALB/c) were subjected to subpatellar puncture. HypoBALB/c mice were treated with warfarin and anti‐FVIII before injury, after which warfarin was continued for 2 weeks or reversed +/− continuous anti‐FVIII until harvest. Synovial vascularity was analyzed at baseline and 2 to 4 weeks post injury by histology, musculoskeletal ultrasound with power Doppler (microvascular flow), and Evans blue extravasation (vascular permeability). Synovial gene expression and systemic markers of vascular collagen turnover were studied in FVIII‐deficient mice by RNA sequencing and enzyme‐linked immunosorbent assay.ResultsVascular changes occurred in FVIII‐deficient and HypoBALB/c mice after injury with minimal effect of hemostasis correction. Increased vascular permeability was only significant in FVIII‐deficient mice, who exhibited more pronounced vascular remodeling than HypoBALB/c mice despite similar bleed volumes. FVIII‐deficient mice exhibited a strong transcriptional response in synovium that was only partially affected by FVIII treatment and involved genes relating to angiogenesis and extracellular matrix remodeling, with vascular collagen turnover markers detected systemically.ConclusionsIntact hemostasis at the time of hemarthrosis and during healing are both critical to prevent vascular remodeling, which appears worse with severe and prolonged FVIII deficiency. Unbiased RNA sequencing revealed potential targets for intervention and biomarker development to improve management of HA." @default.
• W2962506670 created "2019-07-23" @default.
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• W2962506670 date "2019-11-01" @default.
• W2962506670 modified "2023-10-16" @default.
• W2962506670 title "Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII‐deficient mice" @default.
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• W2962506670 doi "https://doi.org/10.1111/jth.14567" @default.
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